CA2436741A1 - Aryl substituted alkylcarboxylic acids as hypocholesterolemic agents - Google Patents

Abstract

The present invention relates to novel antiobesity and hypocholesterolemic compounds, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and pharmaceutically acceptable compositions containing them. More particularly, the present invention relat es to novel b-aryl-a-oxysubstituted alkylcarboxylic acids of the general formul a (I), their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and pharmaceutically acceptable compositions containing them.

Description

ARYL SUBSTITUTED ALKYLCARBOXYLIC ACIDS AS HYPOCHOLESTEROLEMIC AGENTS
Field of the Inyention The present invention relates to novel antiobesity and hypocholesterolerriic compounds, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polyrizorphs, . their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and , pharmaceutically acceptable compositions containing theta . More particularly, the present invention relates to novel (3~-aryl-a,-oxysubstituted 1o alkylcarboxylic acids of the general formula (I), their derivatives; their analogs, their tautomeric forms, their stereoisomers, their polyrizorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and pharmaceutically acceptable compositions containing them:

A-(Cf-12)n-~-Ar YR4 ~) 1s The present invention also relates to a process for the preparation of the above said novel compounds, their analogs, their derivatives, their tautorneric forms, their stereoisomers, their' polyrnorphs, their pharmaceutically acceptable salts, pharmaceutically acceptable solvates arid pharmaceutical compositions' containing them.
2o The present invention also relates to novel intermediates, processes for their preparation and their use in the preparation of compounds of formula (I).
The compounds of the present invention lower plasma glucose, triglycerides, lower total cholesterol (TC) and increase high density lipoprotein (HDL) and decrease low density lipbprotein (LDL), which have a beneficial 25 effect on coronary heart disease and atherosclerosis.
The compounds of general formula (I) are useful in reducing body weight and for the treatment and/or prophylaxis of diseases such as atherosclerosis, stroke, peripheral vascular diseases and related disorders.
These compounds are useful for the treatment of hyperglycemia, hyperlipidemia, hypercholesterolemia, lowering of atherogenic lipoproteins, VLDL (very low density lipoprotein) and LDL. The compounds of the present s invention can be used for the treatment of certain renal diseases including glomeruloriephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis and nephropathy. The compounds of general formula (I) are also useful for the treatment and/or prophylaxis of type 2 diabetes, leptin resistance, atherosclerosis, impaired glucose tolerance, disorders related to to syndrome X such as hypertension, obesity, insulin resistance, coronary heart disease and other cardiovascular disorders. These cbxripounds may also be useful as aldose reductase inhibitors, for improving cognitive functions in dementia, treating diabetic complications, disorders related to endothelial cell activation, psoriasis, polycystic ovarian syndroriie (PCOS), inflanunatory 1s bowel diseases, osteoporosis, riiyotonic dystrophy, pancreatitis, arteriosclerosis, retinopathy, xanthoma, eating disorders; inflamriiation and for the treatment of cancer. The compounds of the present invention are also useful in the treatment andlor prophylaxis of the above said diseases in combination/concomittant with one or more HMG CoA reductase inhibitors, 2o hypolipidemic/hypolipoproteinemic agents such as fibric acid derivatives, nicotinic acid, cholestyramine, colestipol and probucol.
Background of the Invention 2s Atherosclerosis and other peripheral vascular diseases axe the major causes effecting the quality of life of rilillions of people. Therefore, considerable attention has been directed towards understanding the etiology of hypercholesterolemia and hyperlipidemia and development of effective therapeutic strategies. .

Hypercholesterolemia has been defined as plasma cholesterol level that exceeds arbitrarily defined value called "normal" level. lZecently, it has been accepted that "ideal" plasma levels of cholesterol are much below the "normal" level of cholesterol in the general population and the risk of coronary artery disease (CAD) increases as cholesterol level rises above the "optimum" (or "ideal") value. There is clearly a definite cause and effect-relationship between hypercholesterolemia and CAD, particularly for individuals with multiple risk factors. Most of the cholesterol is present in the esterified forms with various lipoproteins such as Louw density lipoprotein to (LDL), intermediate density lipoprotein (IDL), giigh density lipoprotein .
(HDL) and partially as Very low density lipoprotein (VLDL). Studies clearly indicate that there is an inverse ~correlationship between CAD and atherosclerosis with serum HDL-cholesterol concentrations. (Stampfer et al., N. Engl. J. lVled., 325 (1991), 373-381) and the risk of CAD increases with increasing levels of LDL and VLDL.
gn CAD, generally "fatty streaks" in carotid, coronary and cerebral arteries, are found which are primarily free and esterified cholesterol.
Miller et al., (Bn. Med. J., 282 (1981), 1741 - 1744) have shovsm that increase in 2o HDL-particles may decrease the number of sites of stenosis in coronary arteries of human, and high level of HDL=cholesterol may protect against the progression of atherosclerosis. Picardo et al., (Arteriosclerosis 6 (1986) 434 -441) have shown by in vitro experiment that HDL is capable of removing cholesterol from cells. They suggest .that HDL may deplete tissues of excess free cholesterol and transfer it to liver (Macikinnon et al., .d Biol. chefn.

(1986), 2548 - 2552). Therefore, agents that increase HDL cholesterol would have therapeutic significance for the- treatment of hypercholesterolernia and coronary heart diseases (CHD).

Obesity is a disease highly prevalent in affluent societies and in the developing world and is a major cause of morbidity and mortality. It is a state of excess body fat accumulation. The causes of obesity are unclear. It is believed to be of genetic origin or promoted by an interaction between the genotype and environment. Irrespective of the cause, the result is fat deposition due to imbalance between the energy intalce versus energy expenditure. Dieting, exercise and appetite suppression have been a part of obesity treatment. There is a need for efficient therapy to fight this disease since it may lead to coronary heart disease, diabetes, stroke, hyperlipidemia, to gout, osteoarthritis, , reduced fertility and many other psychological and social problems.
Diabetes and insulin resistance is yet another disease which severely effects the quality of a large population in the world. Insulin resistance is the diminished ability of insulin to exert its biological action across a broad range t5 of concentrations. In insulin resistance, the body secretes abnormally high amounts of insulin to compensate for this defect; failing which, the plasma glucose concentration inevitably rises and develops into diabetes. Among the developed countries, diabetes mellitus is a common problem and is associated with a variety of abnormalities including obesity, , hypertension, hyper-20 lipidemia (J. Clin. Invest., (1985) 75 : 809 - SI7; N. Engl. J. Med. (I987) 317: 350-357; J. Clin. Endocrinol. Metab., (1988) 66 : 580 - 583; J. Clin.
Invest., (1975) 68 : 957 - 969) and other renal complications (See Patent Application No. WO 95/21608). It is now increasingly being recognized that insulin resistance and relative hyperinsulinemia have a contributory role in 25 obesity, hypertension, atherosclerosis and type 2 diabetes mellitus. The association of insulin resistance with obesity,. hypertension and angina has been described as a syndrome having insulin resistance as the central pathogenic linlc-Syndrome-X.

s Hyperlipiderizia is the primary cause for cardiovascular (CVD) and other peripheral vascular diseases. High risl~ of CVD is related to the higher LDL (Low Density Lipoprotein) and VLDL (Very Low Density Lipoprotein) seen in hyperlipidemia. Patients having glucose intolerance/insulin resistance s in addition to hyperlipidemia have higher risk of CVD. Numerous studies in the past have shown that lowering of plasma triglycerides and total cholesterol, in particular LDL and VLDL and increasing HDL cholesterol help in preventing cardiovascular diseases.
Peroxisome proliferator activated receptors (PPAR) are members of the to nuclear receptor super family. The gamma (y) isoform of PPAR (PPARy) has been implicated im regulating differentiation of adipocytes (Endocrinology, (1994) 135: 798-800) and energy homeostasis (Cell, (1995) 83: 803-812), whereas the alpha (cc) isoform of PPAR (PPARoc) mediates fatty acid oxidation (Trend. Endocrin. Metab., (1993) 4: 291-296) thereby resulting in is reduction of circulatilzg free fatty acid in plasma (Current Biol. (1995) 5: 618 -621). PPARa agonists have been found useful for the treatment of obesity (WO 97/36579). It has been recently disclosed that there exists synergism for the molecules, which are agonists for both PPARa and PPARy and suggested to be useful. for the treatment of syndrome ~ (WO 97/25042). Similar 2o synergism between the insulin sensitizer (PPARy agonist) and HMG CoA
reductase inhibitor has been observed which may be useful for the treatment of atherosclerosis and xanthoma (EP 0 753 298).
It is lmown that PPARy plays an important role in adipocyte differentiation (Cell, (1996) 87, 377-389). Ligand activation of PPAR is 2s sufficient to cause complete terminal differentiation (Cell, (1994) 79, 1156) including cell cycle withdrawal. PPARy is consistently expressed in certain cells and activation of this nuclear receptor with PPARy agonists would stimulate the terminal differentiation of adipocyte precursors and cause morphological and molecular changes characteristics of a more differentiated, less malignant state (Molecular Cell, (1998), 465-470; Carcinogenesis, (1998), 1949-53; Proc. Natl. Acad. Sci., (1997) 94, 237-241) and inhibition of expression of prostate cancer tissue (Cancer Research (1998) 58:3344-3352).
This would be useful in the treatment of certain types of cancer, which express PPARy and could lead to a quite nontoxic chemotherapy.
Leptin resistance is a condition wherein the target cells are unable to respond to leptin signal. This may give rise to obesity due to excess food intal~e and reduced energy expenditure and cause impaired glucose tolerance, type 2 diabetes, cardiovascular diseases and such other interrelated Io complications. Kallen.et al (Proc. Natl. Acad. Sci. (1996) 93, 5793-5796) have reported that insulin sensitizers which perhaps due to the PPAR agonist expression and therefore lower plasma leptin concentrations. However, it has been recently disclosed that compounds having insulin sensitizing property also possess leptin sensitization activity. They lower the circulating plasma is leptin concentrations by improving the target cell response to leptin (W~/98/02159).
A few (3-aryl-a,-hydroxy propionic acids, their derivatives and their analogs have been reported to be useful in the treatment of hyperglycemia and hypercholesterolemia. Some of such compounds described in the prior art are 20 outlined below:
i) U.S. Pat. 5,306,726, WQ 91/19702 discloses several 3-aryl-2-hydroxypropionic acid derivatives of general formulas (IIa) and (IIb) as hypolipidemic and hypoglycemic agents.
X~yZ~ / COY
Z Y A COY
X~~(CH2)n~ \ I 'X~R
X~ R Z
(IIa) ~ Z1 (Idb) 25 Examples of these compounds are shown in formulas (IIc) and (IId) Bn0 COOH
I OEt (IIc) O

COOH
Ph \ ~ \ ~ OEt (IId) N O
ii) International Patent Applications, WO 95/03038 and WO
96/04260 disclose compounds of formula (IIe) COOH
CH3 ~ ~",H
Ra-N~O \ ~ OCH~Rb (IIe) wherein Ra represents 2- benzoxazolyl or 2-pyridyl and Rb represent CF3, CH20CH3 or CH3. A typical example is (~-3-[4-[2-[N-(2-benzoxazolyl)-N-methylamino] ethoxy]phenyl]-2-(2,2,2-trifluoroethoxy)propanoic acid (IIf).
COON
/ N CHa \ I ~-NCO \ ~ OCH2CF3 (IIO
iii) International Patent Application Nos. WO 94/13650, WO
94/01420 and WO 95/17394 disclose the compounds of general formula (IIg) '~X-(CH2)ri O-A2-A3-Y. R2 (IIg) wherein A1 represents aromatic heterocycle, A2 represents substituted is benzene ring and A3 represents a moiety of formula (CH2)m CH-(ORl), wherein R1 represents allcyl groups, m is an integer; X represents substituted or unsubstituted N; Y represents C=O or C=S; R2 represents OR3 where R3 may be alkyl, arallcyl, or aryl group; n represents an integer in the range of 2-6.
An example of these compounds is shown in formula (IIIi) / C02CHzCH3 \ ~ ~N~O \ O~OPh iv) International publication No. WO 99/08501 discloses compounds of general formula (IIi) x Ri _ R4 N ~ Rs O
~ (CHZ)"-O-Ar--' , //
R2 N~R3 ~ YR~ ~') where X represents O or S ; the groups R1, R2 and group R3 when attached s to the carbon atom, may be same or different and represent hydrogen, halogen, hydroxy, nitro, cyano, fonnyl or optionally substituted groups selected from alkyl, cycloallcyl, allcoxy, cycloallcoxy, aryl, aryloxy, arallcyl, aralkoxy, heterocyclyl, heteroaryl, heteroarall~yl; heteroaryloxy, heteroaralkoxy, aryl, acyloxy, hydroxyallcyl, amino, acylamino, allcylamino, arylamino, aralkylamino, aminoalkyl, allcoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyall~yl, aryloxyallcyl, arallcoxyalkyl, allcylthio, thioalkyl, ~ allcoxycarbonylamino, aryloxycarbonylamino, arallcoxycarbonylamino, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R1, R~ along with the adjacent atoms to which they are 1s attached may also form a 5-6 membered substituted or unsubstituted cyclic structure containing carbon atoms with one or more double bonds, which may optionally contain one or more heteroatoms selected from oxygen, nitrogen and sulfur; R3 when attached to nitrogen atom represents hydrogen, hydroxy, . formyl or optionally substituted groups selected from allcyl, cycloalkyl, 2o alkoxy, cycloallcoxy, aryl, aralkyl, heterocyclyl, heteroaryl, heteroaralkyl, acyl, acyloxy, hydroxyalkyl, amino, acylamino, allcylamino, arylamino, aralkylamino, aminoallcyl, aryloxy, arallcoxy, heteroaryloxy, heteroaralkoxy, allcoxycarbonyl, aryloxycarbonyl, arallcoxycarbonyl, alkoxyalkyl, aryloxyallcyl, arallcoxyallcyl, allcylthio, thioallcyl groups, carboxylic acid 2s derivatives, or sulfonic acid derivatives; the linking group represented by (CH2)n-O- may be attached either through nitrogen atom or through carbon atom where n is an integer ranging .from 1 - 4; Ar represents an optionally substituted divalent single or fused aromatic or heterocyclic group; R4 represents hydrogen atom, hydroxy, allcoxy, halogen, lower alkyl, optionally substituted aralkyl group or forms a bond together with the adjacent group RS;
RS represents hydrogen, hydroxy, alkoxy, halogen, lower allcyl group, acyl, s optionally substituted arallcyl or RS forms a bond together with R4; R6 may be hydrogen, optionally substituted groups selected from allryl, cycloalkyl, aryl, aralkyl, allcoxyall~yl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl, acyl, heterocyclyl, heteroaryl, heteroaralkyl groups, with a provision that R6 does not represent hydrogen when R7 represents hydrogen or to lower allcyl group; R7 may be hydrogen or optionally substituted groups selected from allcyl, cycloallcyl, aryl, arallcyl, heterocyclyl, heteroaryl, heteroarallcyl groups; Y represents oxygen or NRg, where R8 represents hydrogen, alkyl, aryl, hydroxyallcyl, aralleyl, heterocyclyl, heteroaryl, heteroarallcyl groups; R7 and R8 together may form a substituted or is unsubstituted 5 om 6 membered cyclic structure containing carbon atoms, which may optionally contain one or more heteroatoms selected from oxygen, sulfur or nitrogen.
An example of these compounds is shown in formula (IIj) ~OEt g 2o v) European publication No. EP 0903343 discloses compounds of general formula (IIIc) R COY (Ilk) R ~J
X~R2 W -.A
where A is an allcylene, alkyleneoxy or allcylenecarbonyl, X is O, S, NH or CHZ; YI is an amino, hydroxylamino, hydroxyalkylamino, monoalkylamino, dialkylamino, cyclic amino, hydroxy or lower alkoxy group; R1 is a hydrogen atom, lower alkyl, hydroxyallcyl group, allcoxyallcyl, halogenallcyl or COY2, where Y2 is amino, ~hydroxyamino, hydroxyalkylamino, monoalkylamino, dialkylamino, cyclic amino, hydroxy or lower allcoxy group; Ra is lower alkyl, s hydroxyalkyl, alkoxyallcyl or halogenalkyl group, COY2or a phenyl, pyridyl or aralkyl which may be substituted and R3 is a hydrogen or halogen, allcyl, allcoxy, halogenallcyl, amino, hydroxy or acyl groups or a salt thereof; W is a monocyclic or cyclic lactam ring selected from the following groups which may be substituted \ \ w \ N I
(R4)m I / N~ (R4)m ! / N~ (R4)m i / N. s O R
O
Z~ O N. N
Ra ~ \ ~ \ Z ~ Ra t \ i ( )m- / N
( )m i / N\ (R4)m i / N
O
O . O Rs R6 ~N- R ~N~ N N s.0 N Nw 10 O R~ O
wherein R4 is a hydrogen, halogen, alkyl, alkoxy, halogenalleyl, amino, hydroxy, cyano, carbonyl, aryl, nitro, carboxy or sulfonamide, phenyl or benzyl which may be substituted; RS is a hydrogen, allcyl, aryl, arallcyl or pyridyl which may be substituted; R6 is hydrogen or lower alkyl group R' is a is lower alkyl, phenyl or arallcyl groups; Zl is O, S, CHI or NRS, ZZ is N or CH
and m is an iilteger of 1 to 4.
An example of these compounds is shown in formula (IIl) H
N
\ ~ _ O (111) / NCO \ / OH

Summary of the Invention With an objective to develop novel compounds for lowering cholesterol s and reducing body weight with beneficial effects in the treatment and/or prophylaxis of diseases related to increased levels of lipids, atherosclerosis, coronary artery diseases, Syndrome-X, impaired glucose tolerance, insulin resistance, insulin ~ resistance leading to type 2 diabetes and diabetes complications thereof, for the treatment of diseases wherein insulin resistance to is the pathophysiological mechanism and for the treatment of hypertension, with better efficacy, potency and lower toxicity, we focused our research to develop new compounds effective in the treatment of the above mentioned diseases. Effort in this direction has led to compounds having general formula (I).
is 'The main objective of the present invention is therefore, to provide novel (3-aryl-a-oxysubstituted allrylcarboxylic acids, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and pharmaceutical compositions containing them, or their mixtures.
2o Another objective of the present invention is to provide novel (3-aryl-a,-oxysubstituted allcylcarboxylic acids, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and pharmaceutical compositions containing them or their mixtures which 25 may have agonist activity against PPARa and/or PPARy, and optionally iilhibit I-IMCg CoA reductase, in addition to having agonist activity against PPARa, and/or PPARy.
Another objective of the present invention is to provide novel ~-aryl-a-oxysubstituted allcylcarboxylic acids, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates ~d pharmaceutical compositions containing them or their mixtures having enhanced activities, without toxic effect or with reduced toxic effect.
Yet another objective of the present invention is a process for the preparation of novel (3-aryl-a-oxysubstituted alkylcarboxylic acids of formula (I), their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts and their pharmaceutically acceptable solvates.
to Still another objective of the present invention is to provide pharmaceutical compositions containing compounds of the general formula (I), their analogs, their derivatives, their tautomers, their stereoisomers, their polymorphs, their salts, solvates or their mixtures in combination with suitable carriers, solvents, diluents and other media normally employed in preparing such compositions.
Another objective of the present invention is to provide novel intermediates, a process for their preparation and their use in the preparation of j3-aryl-oc-oxysubstituted alkyl carboxylic acids of formula (I), their derivatives, their analogs; their tautomers, their stereoisomers, their polynozphs, their salts 2o and their pharmaceutically acceptable solvates.
Detailed Description of the Invention (3-aryl a-oxysubstituted propionic acids, their derivatives and their 2s analogs of the present invention have the general formula (I) R~ O
A-(CH2)n-~-Ar where R1 represents hydrogen atom, halogen, hydroxy, lower alkyl, alkoxy, substituted or unsubstituted arallcyl group or forms a bond together with the adjacent group RZ; RZ represents hydrogen, hydroxy, halogen, lower alkyl, alkoxy, alkanoyl, amyl, aralkanoyl, substituted or unsubstituted aralkyl or R2 forms a bond together with Rl; R3 may be hydrogen atom or substituted or unsubstituted groups selected from alkyl, cycloallcyl, aryl, allcanoyl, aroyl, arallryl, heterocyclyl, heteroaryl, heteroarallcyl, allcoxyalkyl, allcoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl groups, with a provision that R3 does not represent hydrogen when R4 represents hydrogen or to lower allcyl group; R4 may be hydrogen or substituted or unsubstituted groups selected from alkyl, cycloallcyl, aryl, arallcyl, heterocyclyl, heteroaryl or heteroarallcyl groups; Y represents oxygen or NF.S, where RS represents hydrogen or substituted or unsubstituted groups selected from alkyl, aryl, arallcyl, hydroxyallcyl, alkanoyl, amyl, arallcanoyl, heterocyclyl, heteroaryl or heteroaralkyl groups; R4 and RS together may form a substituted or unsubstituted 5 or 6 membered cyclic structure containing carbon atoms, a nitrogen atom and which may optionally contain one or more additional heteroatoms selected from oxygen, sulfur or nitrogen; n is aal integer ranging from 1- 4; Ar represents substituted or unsubstituted, divalent, single or fused, 2o aromatic or heterocyclic group; A represents a cyclic structure given below X X X X
R7 N I N ' R~ ~S I N R~ ~ I N R ~N N
~! 6 ~ N'\ 6 ~ I NW6 $ ~ ~ N~ 6 Rs N R Rs R R$ R R R
X X X X "
R~~N ~ N R NON ~ N R~~~ N R~~~ N
a ° i ~(~ ~° ~ ~~ ~° ~ ~ f N N~CR6 Rs N R6 Rs S N. Rs R$ N N. R6 X X X X
R~ ~ N R7 N N R7 N N R7 N N
_. ' _. ' _. ~ _.
g ~ ~ %\(~ 6 S ~ ~~ 6 O ~ N'\, 6 RO /N ~ ~~ 6 R N R N R R N R
X X x X x N R~~N N Rw _N R~~N~ N R~~N~ N
\ ~ ~ O. SAi xi 'N I ~~Rs Ra N I NxRs CN NXRs Rs ~ NxRs R$ N Rs where X represents O or S; R6 when attached to the carbon atom represents hydrogen, halogen, hydroxy, vitro, cyano, formyl or substituted or unsubstituted groups selected from allcyl, cycloallcyl, allcoxy, cycloalkoxy, aryl, aryloxy, aralkyl, arallcoxy, heterocyclyi, heteroaryl, heteroaraix-yl, heteroaryloxy, heteroarallcoxy, allcanoyl, amyl, alkanoyloxy, hydroxyallcyl, amino, acylamino, monoallcylamino, diallcylamino, arylamino, arallcylainino, aminoallcyl, alleoxycarbonyl, aryloxycarbonyl, arallcoxycarbonyl, alkoxyalkyl, aryloxyalkyl, arallcoxyalkyl, alkylthio, thioallcyl, alkoxycarbonylamino, to aryloxycarbonylamino, arallcoxycarbonylamino, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R~ when attached to nitrogen atom represents hydrogen, hydroxy, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, allcoxy, cycloalkoxy, aryl, aralkyl, aryloxy, arallcoxy, heterocyclyl, l2eteroaryl, heteroaralkyl, heteroaryloxy, heteroarallcoxy, alkanoyl, amyl, alkanoyloxy, hydroxyalkyl, ammo, acylamino, monoallcylamino, diallcylamino, arylamino, aralkylamino, aminoalkyl, allcoxycarbonyl, aryloxycarbonyl, arallcoxycarbonyl, allcoxyalkyl, aryloxyalkyl, arallcoxyallcyl, allcylthio, thioalkyl groups, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R7 and R8 when attached to 2o carbon atom may be same or different and represent hydrogen, halogen, hydroxy, cyano, vitro, formyl or substituted or unsubstituted groups selected from allcyl, all~oxy, aryl, aryloxy, arallcyl, arallcoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, allcoxyalkyl, thioalkyl, alkylthio groups;
R' and R$ when attached to nitrogen may be same or different and represent hydrogen, hydroxy or substituted or unsubstituted groups selected from alkyl, s alkoxy, aryl, aryloxy, arallcyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyallcyl, amino, monoalkylamino, diallcylamino, arylamino groups.
Suitable groups represented Rl may be selected from hydrogen, hydroxy, halogen atom such as fluorine, chlorine, bromine or iodine; lower to alkyl groups such as methyl, ethyl, propyl and the like; (Cl-C3)alkoxy such as methoxy, ethoxy, propoxy and the like; substituted or unsubstituted aralkyl such as benzyl, phenethyl and the like or Rl together with R2 represent a bond.
When the aralkyl group is substituted, the substituents may be selected from hydroxy, halogen atom, nitro or amino groups.
is Suitable groups represented RZ may be selected from hydrogen, hydroxy, halogen atom such as fluorine, chlorine, bromine, iodine; lower alkyl groups such as methyl, ethyl, propyl and the like; (C~-C3)allcoxy such as methoxy, ethoxy, propoxy and the like; linear or branched (CZ-Clo)alkanoyl group such as acetyl, propanoyl, butanoyl, pentanoyl and the like; amyl such 2o as benzoyl, substituted benzoyl and the like; arallcanoyl groups such as phenylacetyl, phenylpropanoyl and the like; substituted or unsubstituted aralkyl such as benzyl, phenethyl and the like or R2 together with Rl forms a bond. The substituents may be selected from hydroxy, halogen, nitro, amino groups.
2s It is preferred that Rl and Ra represent hydrogen atom or Rl and R2 together represent a bond.
Suitable groups represented by R3 may be selected from hydrogen, substituted or unsubstituted, linear or branched (C1-C16)allcyl, preferably (C1-C12)alkyl group such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, pentyl, hexyl, octyl and the liice; substituted or unsubstituted, linear or branched(Ca-C16)allcanoyl group such as acetyl, propanoyl, butanoyl, octarmyl, decanoyl and the like; amyl such as benzoyl, substituted benzoyl and the like;
(C3-C7)cycloallcyl group such as cyclopropyl, cyclobutyl, cyclopentyl, s cyclohexyl, and the lilce, the cycloalkyl group may be substituted; aryl group such as phenyl, naphthyl and the like, the aryl group may be substituted;
aralkyl such as benzyl, phenethyl, CGHSCI~~CH2CHa, naphthylinethyl and the like, the aralkyl group may be substituted and the substituted aralkyl is a group such aS C~I3C6~-I4CPI2, ~Ial-C6H4CH2, CH3OC6H4CH2, CH3OC6H4CddZCH2 and to the like; heterocyclyl group such as aziridinyl, pyrrolidinyl, piperidinyl and the like, the ,,heterocyclyl group may be substituted; heteroaryl group such as pyridyl, thienyl, furyl and the lilce, the heteroaryl group may be substituted;
heteroarallcyl group such as furamnethyl, pyridinemethyl, oxazolemethyl, oxazolethyl and the lilce, the heteroarallcyl group may be substituted; (C1-ls C6)allcoxy(C1-C6)allcyl group such as methoxymethyl, ethoxymethyl, methoxyethyl, ethoxypropyl and the like, the alkoxyallcyl group may be substituted; (Cl-C6)alkoxycarbonyl such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl and the like, which may be substituted; aryloxycarbonyl such as phenoxycarbonyl, naphthyloxycarbonyl and the like, which may be 20 ~ substituted; (Cl-C6)allcylamiilocarbonyl such as methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl and the like, which may be substituted; arylaminocarbonyl such as PhNHC~, naphthylaminocarbonyl and the like, which may be substituted. The substituents may be selected from halogen, hydroxy oar nitro or substituted or unsubstituted groups selected from 2s alkyl, cycloalkyl, allcoxy, cycloallcoxy, aryl, aralkyl, aralkoxyalkyl, heterocyclyl, heteroaryl, heteroarallcyl, allcanoyl, allcanoyloxy, hydroxyalkyl, amino, acylamino, arylamino, aminoallcyl, aryloxy, alkoxycarbonyl, alkylamino, allcoxyalkyl, alkylthio, thioallcyl groups, carboxylic acid or its derivatives, or sulfonic acid or its derivatives.

Suitable groups represented by R4 may be selected from hydrogen, substituted or unsubstituted, linear or branched (Cl-C16)alkyl, preferably (C1-Clz)allcyl group such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, pentyl, hexyl, octyl and the like; (C3-C7)cycloallcyl such as cyclopropyl, cyclopentyl, cyclohexyl and the like, the cycloallcyl group may be substituted;
aryl group such as phenyl, naphthyl and the like, the aryl group may be substituted; arallcyl group such as benzyl, phenethyl and the like, the aralkyl group may be substituted; heterocyclyl group such as aziridinyl, pyrrolidinyl, piperidinyl and the like, the heterocyclyl group may be substituted;
heteroaryl to group such as pyridyl, thienyl, furyl and the lilce, the heteroaryl group may be substituted; heteroarallcyl group such as furanmethyl, pyridinemethyl, oxazolemethyl, oxazolethyl and the like, the heteroaralkyl group may be substituted. The substituents on R4 may be selected from the same group of R7 and Rg.
Suitable Y represents oxygen or NRS.
Suitable groups represented by RS may be selected from hydrogen, substituted or unsubstituted, linear or branched (Ct-C16)allcyl, especially, (C~-Clz)allryl group, such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, t-butyl, n-pentyl, iso-pentyl, hexyl, heptyl, octyl and the like; aryl group such 2o as phenyl, naphthyl and the lilce, the aryl group may be substituted;
hydroxy(C1-C6)allcyl, which may be substituted; substituted or unsubstituted, linear or branched(Cz-C6)allcanoyl group such as acetyl, propanoyl, butanoyl and the like; arallcyl group such as benzyl, phenethyl and the like, the aralkyl groups may be substituted; aroyl such as benzoyl, substituted benzoyl and the like; arallcanoyl groups such as phenylacetyl, phenylpropanoyl and the like, which may be substituted; heterocyclyl group such as aziridinyl, pyrrolidinyl, piperidinyl, and the like, the heterocyclyl group may be substituted;
heteroaryl group such as pyridyl, thienyl, furyl and the like, the heteroaryl group may be substituted; heteroaralkyl group such as furanmethyl; pyridinemethyl, oxazolemethyl, oxazolethyl and the like, the heteroaralkyl group may be substituted. The substituents may be selected from halogen, hydroxy, amino, vitro or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, aryl, arallcyl group.
Suitable ring structures formed by R4 and RS together may be selected from pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, oxazolinyl, diazolinyl and the like.
Suitable substituents on the cyclic structure formed by R4 and RS taken together may be selected from halogen, hydroxy, alkyl, oxo, aralkyl and the like.
Suitable n is an integer ranging from 1 to 4, preferably n represents an integer of 1 or 2.
Suitable groups represented by Ar include substituted or unsubstituted groups selected from divalent phenylene, naphthylene, pyridyl, quinolinyl, is benzofuryl, dihydrobenzofuryl, benzopyranyl, indolyl, indolinyl, azaindolyl,~
azaindolinyl, pyrazolyl, ~ benzothiazolyl, benzoxazolyl and the like. The substituents on the group represented by Ar may be selected from optionally halogenated substituted or unsubstituted linear or branched (C~-C6)alkyl, optionally halogenated (C~-C3)allcoxy, halogen, alkanoyl, amino, acylamino, 2o thio or carboxylic or sulfonic acids and their derivatives.
It is preferred that Ar represents substituted or unsubstituted divalent phenylene, naphthylene, benzofuryl, indolyl, indolinyl, quinolinyl, azaindolyl, azaindolinyl, benzothiazolyl or benzoxazolyl.
It is more preferred that Ar is represented by divalent phenylene or 25 naphthylene, which may be substituted or unsubstituted by methyl, halomethyl, methoxy or halomethoxy groups.
Suitable groups represented by R6 when attached to carbon atom may be selected from hydrogen, halogen atom such as fluorine, chlorine, bromine, or iodine; hydroxy, cyano, vitro, formyl; substituted or unsubstituted (C1-C12)alkyl group, especially, linear or branched (C~-Clo)alkyl group, such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, t-butyl, n-pentyl, iso-pentyl, hexyl, heptyl, octyl and the like; cyclo(C3-C6)alkyl group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like, the cycloalkyl s group may be substituted; (C~-C6)allcoxy such as methoxy, ethoxy, propyloxy, butyloxy, iso-propyloxy and the like, the allcoxy group may be substituted;
cyclo(C3-C6)alleoxy group such as cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy and the lilce, the cycloallcoxy group may be substituted; aryl group such as phenyl, naphthyl and the like, the aryl group to may be substituted; aryloxy group such as phenoxy, naphthyloxy and the like, the aryloxy group may be substituted; aralkyl such as benzyl, phenethyl, C6HSCH2CHZCH2, naphthylmethyl and the lilce, the arallcyl group may be substituted and the substituted arallcyl is a group such as CH3C6H4CH2, Hal-C6H4CHa, CH3OC6H4CH2, CH30CsH4CHZCH2 and the like; aralkoxy group is such as benzyloxy, phenethyloxy, naphthylmethyloxy, phenylpropyloxy and the lilce, the aralkoxy group may be substituted; heterocyclyl groups such as aziridinyl, pyrrolidinyl, morpholinyl, piperidinyl, piperazinyl and the lilce, the heterocyclyl group may be substituted; heteroaryl group such as pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, oxadiazolyl, tetrazolyl, 2o benzopyranyl, benzofuranyl and the like, the heteroaryl group may be substituted; heteroarallcyl group such as furanmethyl, pyridinemethyl, oxazolemethyl, oxazolethyl and the like, the heteroaralkyl group may be substituted; heteroaryloxy and heteroarallcoxy, wherein heteroaryl and heteroaralkyl moieties are as defined earlier and may be substituted; alkanoyl 2s group such as acetyl, propionyl and the like, the allcanoyl .group may be substituted; amyl such as benzoyl, substituted benzoyl and the like;
alkanoyloxy group such as OOCMe, OOCEt, OOCPh and the like which may be substituted; hydroxy(Cl-C6)allcyl, which may be substituted; amino;
acylamino groups such as NHCOCH3, NHCOC2H5, NHCOC3H7, NHCOC6H5, which may be substituted; mono(CI-C6)allcylamino group such as NHCH3, NHC2H5, NHC3H7, NHC6Hl3 and the like, which may be substituted; (C1-C6)dialkylamino group such as N(CH3)z, NCH3(CzHs)and the like, which may be substituted; arylamino group such as HNC6H5, NCH3(C6H5), NHC6H4CH3, s NHC6H4-Hal and the like, which may be substituted; arallcylamino group such as C6HSCHzNH, C6HSCHzCHzNH, C~HsCHaNCH3 and the like, which may be substituted; amino(C1-C6)allcyl, which may be substituted; allcoxycarbonyl such as methoxycarbonyl, ethoxycarbonyl and the like, which may be substituted; aryloxycarbonyl group such as phenoxycarbonyl, to naphthyloxycarbonyl and the like, which may be substituted;
arallcoxycarbonyl group such as, benzyloxycarbonyl, phenethyloxycarbonyl, naphthylmethoxycaxbonyl and the lilce, which may be substituted; allcoxyallcyl group such as methoxymethyl, ethoxymethyl, methoxyethyl, ethoxyethyl and the like, the allcoxyallcyl groups may be substituted; axyloxyalkyl group such is as C6HSOCHz, C6HSOCHzCHz, naphthyloxymethyl and the like, which may be substituted; arallcoxyallcyl group such as C6HSCHzOCHz, C6HSCHzOCHzCHz and the like, which may be substituted; thio(C1-C6)alkyl, which may be substituted; (C~-C6)alkylthio, which may be substituted; alkoxycarbonylamino group such as NHCOOCZHS, NHCOOCH3 and the like, which may be 2o substituted; aryloxycarbonylamino group such as NHCOOC6HSa N(CH3)COOC6H5, N(CZHS)COOC6H5, NHCOOC6H4CH3, NHCOOC6HøOCH3 and the like, which .may be substituted;
aralkoxycarbonylamino group such as NHCOOCH2C6H5, NHC~~CHZCH2C~H5, N(CH3)COOCHZC6H5, N(CzHs)COOCH2C6H5, 2s NHCOOCHzC6H4CH3, NHCOOCHzC6H4OCH3 and the like, which may be substituted; carboxylic acid or its derivatives such as amides, like CONHz, CONHMe, CONMez, CONHEt, CONEtz, CONHPh and the like, or esters such as COOCH3, . COOCZHS, COOC3H7 and the like, the carboxylic acid derivatives may be substituted; sulfonic acid or its derivatives such as SO2NH2, SOZNHMe, S02NMea, SOZNHCF3 and the like, or esters such as COOCH3, COOC2H5, COOC3H7 and the like, the sulfonic acid derivatives may be substituted.
When the groups represented by R6 attached to carbon atom are substituted, the substituents may be selected from halogen, hydroxy, nitro or substituted or unsubstituted groups selected from allcyl, cycloalkyl, alkoxy, cycloallcoxy, aryl, arallcyl, aryloxy, arallcoxy, arallcoxyalkyl, heterocyclyl, heteroaryl, heteroarallcyl, allcanoyl, allcanoyloxy, hydroxyalkyl, amino, acylamino, arylamino, aminoallcyl, allcoxycarbonyl, allcylamino, alkoxyalkyl, to alkylthio, thioalkyl groups, carboxylic acid or its derivatives or sulfonic acid or its derivatives.
It is preferred that the substituents on R6 represents halogen atom such as fluorine, chlorine, bromine, hydroxy group, optionally halogenated groups selected from alkyl group such as methyl, ethyl, isopropyl, n-propyl, n-butyl;
cycloallcyl group such as cyclopropyl; aryl group such as phenyl; aralkyl group such as benzyl; (C1-C3)allcoxy, benzyloxy, alkanoyl or alkanoyloxy groups.
Suitable groups represented by R6 when attached to nitrogen atom may be selected from hydrogen, hydroxy, formyl; substituted or unsubstituted (CI
2o C12)alkyl group, especially, linear or branched (C~-C~)allcyl group, such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, t-butyl, n-pentyl, iso-pentyl, hexyl and the like; cyclo(C3-C6)allcyl group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like, the cycloalkyl group may be substituted; (Cl-C6)allcoxy such as methoxy, ethoxy, propyloxy, butyloxy, iso-2s propyloxy and the like, the allcoxy group may be substituted; cyclo(C3-C6)alkoxy group such as cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, cyclohexyloxy and the like, the cycloallcoxy group may be substituted; aryl group such as phenyl, naphthyl and the like, the aryl group may be substituted;
aryloxy group such as phenoxy, naphthyloxy and the like, the aryloxy group may be substituted; aralkyl such as benzyl, phenethyl, C6H5CH2CH2CH2, naphthylmethyl and the like, the aralkyl group may be substituted and the substituted aralkyl is a group such as CH3C6H4CH2, Hal-C6H4CHz, CH3OC6H4CH2, CH30C6H4CHZCHz and the like; aralkoxy group such as s benzyloxy, phenethyloxy, naphthylmethyloxy, phenylpropyloxy and the like, the aralkoxy group may be substituted; heterocyclyl groups such as aziridinyl, pyrrolidinyl, morpholinyl, piperidinyl, piperazinyl and the like, the heterocyclyl group, may be substituted; heteroaryl group such as pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, oxadiazolyl, tetrazolyl, to benzopyranyl, benzofuranyl and the lilce, the heteroaryl group may be substituted; heteroarallcyl group such as furanmethyl, pyridinemethyl, oxazolemethyl, oxazolethyl and the lilce, the iieteroaralkyl group may be substituted; heteroaryloxy and heteroarallcoxy, wherein heteroaryl and heteroaralkyl moieties are as defined earlier and may be substituted; alkanoyl 1s group such as acetyl, propionyl and the like, the alkanoyl group may be substituted; aroyl such as benzoyl, substituted benzoyl and the like;
alkanoyloxy group such as OOCMe, OOC~t, OOCPh and the like which may be substituted; hydroxy(C1-C6)allcyl, which may be substituted; amino;
acylamino groups such as NHCOCH3, NHCOCZHS, NHCOC3H7, NHCOC6H5, 2o which may be substituted; mono(CI-C6)allcylamino group such as NHCH3, NHC2H5, NHC3H7, NHC6Hl3 and the like, which may be substituted; (C1-C6)dialkylamino group such as N(CH3)2, NCH3(C2H5)and the lilce, which may be substituted; arylamino group such as HNC6H5, NCH3(C6H5), NHC6H4CH3, NHC6H4-Hal and the like, which may be substituted; aralkylamino group such 2s as C6H5CHaNH, C6HSCHZCHZNH, C6HsCH2NCH3 and the like, which may be substituted; amino(Cl-C6)alkyl, which may be substituted; allcoxycarbonyl such as methoxycarbonyl, ethoxycarbonyl and the lilce, which may be substituted; aryloxycarbonyl group such as phenoxycarbonyl, naphthyloxycarbonyl and the lilce, which may be substituted;

aralkoxycarbonyl group such as benzyloxycarbonyl, phenethyloxycarbonyl, naphthylinethoxycarbonyl and the like, which may be substituted; alkoxyalkyl group such as methoxymethyl, ethoxymethyl, methoxyethyl, ethoxyethyl and the lilce, the alkoxyallcyl groups may be substituted; aryloxyallcyl group such s as C6HSOCH2, C6HSOCHZCH2, naphthyloxymethyl and the lilce, which may be substituted; aralkoxyallcyl group such as C6HsCHaOCH2, C6HsCH2OCH2CH2 and the like, which may be substituted; thio(Ct-C6)alkyl, which may be substituted; (CI-C6)alleylthio, which may be substituted; carboxylic acid or its derivatives such as amides, lilce CONH2, CONHMe, CONMe2, CONHEt, to CONEt2, CONHPh and the like, the carboxylic acid derivatives may be substituted; sulfonic acid or its derivatives such as SOZNHZ, SOaNHMe, SOZNMe2, SOZNHCF3 and the lilce, the sulfonic acid derivatives mdy be substituted.
~7Vhen the groups represented by R6 attached to nitrogen are substituted, Is preferred substituents may be selected from halogen such as fluorine, chlorine;
hydroxy, allcanoyl, alkanoyloxy, amino groups.
Suitable groups represented by R' and R$ when attached to carbon atom may be selected from hydrogen, halogen atom such as fluorine, chlorine, bromine, or iodine; hydroxy, cyano, nitro, formyl; substituted or unsubstituted 20 (C~-C12)allcyl group, especially, linear or branched (C~-Clo)alkyl group, such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, t-butyl, n-pentyl, iso-pentyl, hexyl, heptyl, octyl and the like; (Cl-C6)alkoxy such as methoxy, ethoxy, propyloxy, butyloxy, iso-propyloxy and the likes the alkoxy group may be substituted; aryl group such as phenyl, naphthyl and the like, the aryl 2s group may be substituted; aryloxy group such as phenoxy and the like, the aryloxy group may be substituted; arallcyl such as benzyl, phenethyl, C6HSCHaCH2CHa, and the like, the arallcyl group may be substituted and the substituted arall~yl is a group such . as CH3C6H4CH2, Hal-C6H4CH2, CH30C6H4CHz, CH30C6H4CH2CHz and the like; aralkoxy group such as benzyloxy, phenethyloxy, phenylpropyloxy and the like, the aralleoxy group may be substituted; heterocyclyl groups such as aziridinyl, pyrrolidinyl, morpholinyl, piperidinyl, piperazinyl and the like, the heterocyclyl group may be substituted; heteroaryl group such as pyridyl, thienyl, furyl, pyrrolyl, s oxazolyl, thiazolyl, imidazolyl, oxadiazolyl, tetrazolyl, benzopyranyl, . benzofuranyl and the like, the heteroaryl group may be substituted;
heteroaxallcyl group such as furanmethyl, pyridinemethyl, oxazolemethyl, oxazolethyl and the lilee, the heteroarallcyl group may be substituted;
hydroxy(C1-C6)allryl, which may be substituted; amino; mono(C1 1o C6)allcylamino group such as NHCH3, NHCZHs, NHC3H7, NHC6H13 and the lilce, which may be substituted; (C~-C6)diallrylamino group such as N(CH3)z, NCH3(CZHs)and the like, which may be substit'ated; arylamino group such as HNC6Hs, NCH3(C6Hs), NHC6H4CH3, NHC6H4-Hal and the like, which may be substituted; arallcylamino group such as C~HSCHZNH, C6HSCHaCH2NH, Is C6HSCH2NCH3 and the lilce, which may be substituted; amino(C1-C6)alkyl, which may be substituted; allcoxyallcyl group such as methoxymethyl, ethoxymethyl, methoxyethyl, ethoxyethyl and the lilce, the alkoxyalkyl groups may be substituted; thio(Ct-C6)allcyl, which may be substituted; (CI-C6)alkylthio, which may be substituted.
2o When the groups represented by R7 and R8 attached to carbon atom are substituted, the substituent may be selected from halogen, hydroxy, nitro or substituted or unsubstituted groups selected from allcyl, cycloallcyl, allcoxy, cycloalkoxy, aryl, arallcyl, aryloxy, arallcoxy, aralkoxyalkyl, heterocyclyl, heteroaryl, heteroarallcyl, hydroxyallcyl, amino, arylamino, aminoalkyl, 2s alkylamino, allcoxyallcyl, allcylthio, thioallcyl groups, carboxylic acid or sulfonic acid.
It is preferred that the substituent on R7 and R$ represent halogen atom such as fluoride, chlorine or bromine; hydroxy group, optionally halogenated groups selected from alkyl group such as methyl, ethyl, isopropyl, n-propyl, n-butyl and the like; cycloallcyl group such as cyclopropyl; aryl group such as phenyl; arallcyl group such as benzyl; (CI-C3)allcoxy or benzyloxy groups.
Suitable groups represented by R7 and R8 when attached to nitrogen atom may be selected from hydrogen, hydroxy, substituted or unsubstituted s (C~-C~2)allcyl group, especially, linear or branched (CI-Clo)alkyl group, such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, t-butyl, n-pentyl, iso-pentyl, hexyl, heptyl, octyl and the like; (CI-C6)alkoxy such as methoxy, ethoxy, propyloxy, butyloxy, iso-propyloxy and the like, the alkoxy group may be substituted; aryl group such as phenyl and the like, the aryl group may 1o be substituted; aryloxy group such as phenoxy and the like, the aryloxy group may be substituted; arallryl such as benzyl, phenethyl, C6HSCHaCHaCH2 and the lilce, the arallryl group may be substituted and the substituted arallcyl is a group such as CH3C6HqCHz, Hal-C6H4CH2, CH3OC6H4CH2, CH3~C6H4CH2CH2 and the like; arallcoxy group such as benzyloxy, is phenethyloxy, phenylpropyloxy and the lilee, the arallcoxy group may be substituted; heterocyclyl groups such as aziridinyl, pyrrolidinyl, morpholinyl, piperidinyl, piperazinyl and the lilce, the heterocyclyl group may be substituted; heteroaryl group such as pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, oxadiazolyl, tetrazolyl, benzopyranyl, benzofuranyl and 2o the like, the heteroaryl group may be substituted; heteroaralkyl group such as furanmethyl, pyridiizemethyl, oxazolemethyl, oxazolethyl and the like, the heteroarallcyl group may be substituted; hydro xy(C1-C6)allcyl, which may be substituted; amino; mono(Cl-C6)allcylamino group such as NHCH3, NHC2H5, .
NHC3H7, NHC~H13 and the lilce, which may be substituted; (C1-2s C6)diallcylamino group such as N(CH3)2, NCH3(CaHS)and the like, which may be substituted; arylamino group such as HNC6H5, NCH3(CsHs), NHC6H~CH3, NHC6H4-Hal and the lilce, which may be substituted.

When the groups represented by R7 and R8 attached to nitrogen are substituted, preferred substituents may be selected from halogen atom such as fluorine, chlorine; hydroxy, alkyl, allcanoyl, allcanoyloxy, amino groups.
When Rl, R2, R3, R4, R5, R6, R~, R8 or Ar are substituted, the substituents are as defined above.
The compounds of formula (I) where R3 represents hydrogen atom and R4 represents hydrogen or lower alkyl groups have been described in our US
patent Nos. 5,885,997 and 5,985,884.
1o Pharmaceutically acceptable salts forming part of this invention include salts of the carboxylic acid moiety such as alkali metal salts like Li, Na, and K
salts; alkaline earth metal salts like Ca and Mg salts; salts of organic bases such as diethanolamine, choline and the like; chiral bases like alkylphenylamine, phenyl glycinol and the like, salts of natural amino acids 1s such as lysine, arginine, guanidine, methionine, alanine, valine and the like;
unnatural amino acids such as D-isomers or substituted amino acids;
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, tartrates, maleates, 2o citrates, succinates, palmoates, methanesulphonates, benzoates, ~
salicylates, hydroxynaphthoates, benzenesulfon~ates, ascorbates, glycerophosphates, ketoglutarates and the lilce. Pharmaceutically acceptable solvates may be hydrates or comprising other solvents of crystallization such as alcohols.
25 Particularly useful compounds according to the present invention includes:
(~) Ethyl 2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoate ;

(+) Ethyl 2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyri~nidin-6-yl)ethoxy]phenyl]propanoate ;
(-) Ethyl 2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidill-6-yl)ethoxy]phenyl]propanoate ;
(~) 2-Ethoxy 3-[4-[2,-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoic acid or its salts ;
(+) 2-Ethoxy 3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoic acid or its salts ;
to (-) 2-Ethoxy 3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoic acid or its salts ;
(~) Ethyl 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate ;
~s (+) Ethyl 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyriinidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate ;
(-) Ethyl 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidiiz-6-yl)ethoxy]phenyl]-2-ethoxypropanoate ;
20 (~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its salts;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its salts;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-25 d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its salts ;
(~) Ethyl 2-ethoxy-3-[4-[2-(1-methyl-7-oxo-3-propyl-5-trifluoromethyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoate ;

(+) Ethyl 2-ethoxy-3-[4-[2-(1-methyl-7-oXO-3-propyl-5-trifluoromethyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoate ;
(-) Ethyl 2-ethoxy-3-[4-[2-(1-methyl-7-oxo-3-propyl-5-trifluoromethyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoate ;
(~) Ethyl 3-[4-[2-(5-benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate ;
(+) Ethyl 3-[4-[2-(5-benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate ;
to (-) Ethyl 3-[4-[2-(5-benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate ;
(~) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its salts;
1s (+) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its salts;
(-) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its salts;
20 (~) Ethyl 3-[4-[2-(5-benzyl-1-methyl-7-oxo-3-propyl-5,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;
(+) Ethyl 3-[4-[2-(5-benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;
(-) Ethyl 3-[4-[2-(5-benzyl-1-methyl-7-oxo-3-propy1~6,7-dihydro-1H-25 pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;
(~) Ethyl 3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;
(+) Ethyl 3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;
(-) Ethyl 3-[4-[2,-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;
s (~) 3-[4-[2-(5-Ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts;
(+) 3-[4-[2-(5-Ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts;
(-) 3-[4-[2-(5-Ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
' 1o pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts ;
(~) Ethyl 3-[4-[2-(1,5-dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;
(+) Ethyl 3-[4-[2-(1,5-dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-ts d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;
(-) Ethyl 3-[4-[2-(1,5-dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;
(~) 3-[q., [2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
2o pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydra-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoXy]phenyl]-2-phenoxypropanoic acid or its salts ;
2s (~) Ethyl 3-[4-[2-(3,5-dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate ;
(+) Ethyl 3-[4-[2-(3,5-dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate ;

(-) Ethyl 3-[4-[2-(3,5-dipropyl-1-methyl-7-oxo-G,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-G-yl)ethoxy]phenyl]-2-ethoxypropanoate ;
(~) 3-[4-[2-(3,5-Dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-G-yl)ethoxy]phenyl]-2,-ethoxypropanoic acid or its salts;
(+) 3-[4-[2-(3,5-Dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-G-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its salts;
(-) 3-[4-[2-(3,5-Dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-G-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its salts;
to (~) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-G-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts;
(+) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-G-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts;
t5 (-) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-G-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts;
(~) Ethyl 3-[4-[2-(3,5-dipropyl- 1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidill-G-yl)ethoxy]phenyl]-2-phenoxypropanoate ;
20 (+) Ethyl 3-[4-[2-(3,5-dipropyl-1-methyl-7-oxo-G,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-G-yl)ethoxy]phenyl]-2-phenoxypropanoate ;
(-) Ethyl 3-[4-[2-(3,5-dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[~,3-d]pyrimidin-G-yl)ethoxy]phenyl]-2-phenoxypropanoate ;
25 (~) 3-[4-[2-(3,5-Dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-G-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts ;
(+) 3-[4-[2-(3,5-Dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-G-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts ;

(-) 3-[4-[2-(3,5-Dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts;
[2R, N(1S)]-2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-s ' 1H-pyrazolo[4,3-d]pyrimidin-6-y]ethoxy]phenyl]'-N-(2-hydroxy-1-phenylethyl)propanamide and [2S, N(1S)]-2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1 H-pyrazo to [4, 3-d] pyrimidin-6-y] ethoxy]phenyl]-N-(2-hydroxy-1-phenylethyl)propanamide.
to . According to a feature of the present invention, the compound of general formula (I) where Rl and R' together represent a bond, Y represent oxygen atom R3, R4, A, n and Ar are as defined earlier, can be prepared by any of the following roL)tes shown in Scheme-I below.

' A-(CHz)n~0-Ar-CHO ~ R2 (Ilic) + L1-(CHz)n-0-Ar~O
(Ills) a ~'~+
0 (Illd) R30 OR4 090)2 PIcH-(coon4) OR3 (IIIh) ~
(IIIe) y O
A-(CH~)y0-Ar-CHZ-PPh3Hal~ R1 R~ 4 Rz 0 ~OR
(IIIi) + Route 6 A-(CHZ)y0-Ar OR3 O OR .. I 3 / YR4 ~ +
a () RO
O~OR3 ~ A=(CHZ)~ O-Ar-CHO
(IIIj) ~o~ Route 4 (Illa) A-(CH2)n OH RRZ O R z (IIIh) + HO-ArR3~OR4 A-(CH2)nL1 .~. HO-Ar~OR4 (IIIt) (IItg) R3 ~'0 15 (IIIt7 Scheme - I
Route 1 : The reaction ~of a compound of the general formula (IIIa) wl'Iere A, Ar and n are as defined earlier with a compound of foI-mula (IIIb) where R9 represents (C1-C6)allcyl and all other symbols are as defined earlier to yield compound of general formula (I) where all symbols are as defined above may be carried out in the presence of a base such as alkali metal hydrides like NaH
or. KH; organolithiums such as CH3Li, BuLi and the like; allcoxides such as s NaOMe, NaOEt, I~+Bu0- and the lilce or mixtures thereof. The reaction may be carried out in the presence of solvents ,such as THF, dioxane, DMF, DMSO, DME and the like or mixtures thereof. HMPA may be used as . cosolvent. The reaction temperattue may range from -78 °C to 50 °C, preferably at a temperature in the range of -10 °C to 30 °C. The reaction is to more effective under anhydrous conditions. The compound of general formula (IIIb) may be prepared by Arbuzov reaction.
Alternatively, the C0111po1111d of formula (I) may be prepared by reacting the compound of formula (IIIa) where all symbols are as defined earlier with Wittig reagents such as HaIZ'h3P+CH-(OR3)C02R4. udder silnilax reaction ~s conditions as described above.
Route 2 : The reaction of a compound of general formula (IIIc) where A is as defined earlier with a compound of general fonmula (IIId) where L' is a leaving group such as halogen atom, p-toluenesulfonate, methanesulfonate, 2o trifluoromethanesulfonate and the lilce, preferably a halogen atom; Rl, Rz together represent a bond and all other symbols, are as defined earlier to produce a compound of general formula (I) where all symbols are as defined.
above may be carried Ollt in the presence of solvents such as DMSO, DMF, DME, THF, dioxane, ether and the like or mixW res thereof. The reaction may 2s be carried out 111 all lllert at1110Sphere WhlCh may be maintained by using inert gases such as Nz, Ar, He and the lilce. The reaction may be effected in the presence of a base such as alkalis like sodium hydroxide or potassium hydroxide; alkali metal carbonates such as sodilum carbonate or potassium carbonate; alkali metal hydrides such as sodilun hydride or potassium hydride;

organometallic bases like n-butyl lithium; alkali metal amides like sodamide or mixtures thereof. The amount of base may range from 1 to 5 equivalents, based on the amount of the compound of formula (IIIc), preferably the amount of base ranges from 1 to 3 equivalents. Phase transfer catalysts such as s tetraallcylammonimn halide or hydroxide may be added. Additives such as alkali metal halides such as Liar may be added. The reaction may be carried out at a temperatlue in the range of 0 oC to 150 oC, preferably at a temperatl~re in the range of 15 oC to 100 oC. The duration of the reaction may range from 0.25 to 48 hours, preferably from 0.25 to 24 hours.
to Route 3 : The reaction ,of a compound of the general formula (IIIa) where all synbols are as defined earlier, with a compound of formula (IIIe) where R2 represents hydrogen atom and all other symbols are as defined earlier may be carried out in the presence of a base. The nature of the base is not critical.
Any base normally employed for aldol condensation reaction may be employed;
bases like metal hydride such as NaH, I~H, metal allcoxides such as NaOIVIe, t-EuOT~+, NaOEt, metal amides such as LiNHz,~ LiN(ipr)2 may be used. Aprotic solvents such as THF, ether, dioxane may be used. The reaction may be carried out in an inert atmosphere which may be maintained by using inert 2o gases such as N2, Ar, or He and the reaction is more effective under anhydrous conditions. Temperatvue in the range of -80 °C to 35 °C may be used. The (3-hydroxy product ilzitially produced may be dehydrated under conventional dehydration conditions such as treating with pTSA in solvents such as benzene or toluene. The natiue of solvent and dehydrating agent is not 2s critical. Temperatvue in the range of 20 °C to reflex temperature of the solvent used may be employed, preferably at reflex temperature of the solvent by continuous removal of water using a Dean Starlc water separator.

Route 4 : The reaction of C0111pOUtld of fon mina (IIIg) where A and n are as defined earlier aazd L1 represents a leaving group such as halogen atom, p-toluenesulfonate, methanesulfonate, trifluoromethanesulfonate and the like, preferably a halogen atom with compound of formula (IIIf) where Rl and Rz s together represent a bond and all other symbols are as defined earlier to produce a compound of the formula (I) defined above may be carried out in the presence of aprotic solvents such as THF, DMF, DMSO, DME and the lilce or mixtures thereof. The reaction may be carried out in an inert atmosphere which may be maintained by using inert gases such as N2, Ar, He and the like.
to ' The reaction may be effected ll1 the presence of a base such as I~2C03, Na2C03 or NaH or mixtures thereof. Acetone may be used as solvent when NaZC03 or K2C03 is used as a base. The reaction temperature may range from 0 oC - 120 oC, preferably at a temperatiue in the range of 30 oC - 100 oC.
The duration of the reaction may range from 1 to 24 hours, preferably from 2 is to 12 hours. The compound of formula (IIIf) can be prepared according to laiown procedure by a Wittig Horner reaction between the hydroxy protected aryl aldehyde such as benzyloxyaryl aldehyde and compound of formula (IIIb), followed by deprotection.
20 ~ Route 5 : The reaction of compound of general'fornmla (IIIh) where A and n are as defined earlier with a compound of general formula (IIIf) where RI and R2 together represent a bond and all other symbols are as defined earlier may be carried out using suitable coupliilg agents such as dicyclohexyl urea, triarylphosphine/diallcylazadicarboxylate such as 'PPh3 / DEAD and the lilce.
25 The reaction may be carried out in the presence of solvents such as THF, DME, CHZC12, CHCl3, toluene, acetonitrile, carbon tetrachloride and the like.
The inert atmosphere may be maintained by using inert gases such as N2, Ar, He and the like. The reaction may be effected in the presence of DMAP, HOBT and they may be used in the range, of 0.05 to 2 equivalents, preferably 0.25 to 1 equivalents. The reaction temperaW re may be in the range of 0 °C to .
100 °C, preferably at a temperature in the range of 20 °C to 80 °C. The duration of the reaction may range from 0.5 to 24 hours, preferably from ~ to 12 hours.

Route 6 : The reaction of a compound of foxlmula (IIIi) where' all symbols are as~ defined earlier with a compound of formula (IIIj) where R3 = R4 and are as defined earlier excluding hydrogen, to produce a compound ~f the formula (I) where Rl and R2 together represent a bond inay be carried out neat in .the to presence of a base such as alleali metal hydrides like NaH, I~H or organolithiums like CH3Li, BuLi and the like or allcoxides such as NaOh/Ie, NaOEt, t-Bu0-K+ anld the like or mixW res thereof. The reaction may be carried out in the presence of aprotic solvents such as THF, dioxane, DN~F, D1VISO, D1VIE and the lilce or mixtures thereof. HMPA may be used as cosolvent. The 1s reaction temperature may range from -78 °C to 100 °C, preferably at a temperature in the range of -10 °C to 50 °C.
11n yet another embodiment of the present invention, the compound of the general formula (I) where Rl represents hydrogen atom, hydroxy, alkoxy, 2o halogen, lower alkyl, substituted or unsubstituted aralleyl group; R~
represents hydrogen, hydroxy, halogen, lower allcyl, alkoxy, allcanoyl, aroyl, aralkanoyl, substituted or unsubstiW ted arallcyl; R3, R4, n Ar and A are as defined earlier and Y represents oxygen atom can be prepared by one or more of the processes shown in Scheme-II below., R1 z A-(CH~)n-O-Ar L3~OR4 A-(CHZ)n-O-Ar ~ O (IVb) + A-(CHZ)o L~ (IIIg) ~OR4 R30H +
(ZVa) R O Route 8 (IVc) ~y~,o~' HO-Ar R R2 O
R1 dt OlllN? ~-O . R3~OR4 A- CH -O-Ar O (IIIfj ( 2)n ' NOR Routs R1 z' p ' I A-(CHZ)n'OH
~~g) ~. R30H A-(CH2)n-O.-Ar (IVc) 3 YR Route 10 (IIIIb) ~1~ R O ~ 1 +
o~'~' (I) R z O
A-(CH2)n-O-Ar -R~ R~2 ~ , HO-Ar ~CN ~01~ ''~°o~e ~y~'~ORa (IVt) Rs0 ~,o~' Route 12 lI R30° (III
2 O R~ R
A-H (IIIc) R~OR4 A-(CH2)n-O-Ar R ~~~
+ Rz O OR3 (IlIe) OR4 L -(CH2)n-O-Ar-1\I U + (IVY) + HO
\ 4 (IIId) Rs0 OR A-(CH2)n-O-Ar-CHO Rs_Ls (IIIu) ~Ve) Scheme - II
Route 7 : The reduction of compound of the fornlllla (IVa) which represents a s compound of formula (I) where Rl and RZ together represent a bond and ~
represent oxygen atom and all other symbols are as defined earlier, obtained as described earlier(Scheme-I), to yield a compound of, the general formula. (I) where Rl and R2 each represent hydrogen atom and all symbols are as defined earlier, may be carried out in the presence of gaseous hydrogen arld. a catalyst to such as Pd/C, Rh/C, Pt/C, and the lilce. Mixtwes of catalysts may be used.
The reaction may also be conducted in the presence of solvents such as dioxane, acetic acid, ethyl acetate, alcohol such as methanol, ethanol and the like. A
pressure between atmospheric pressure and 80 psi may be employed. The catalyst may be preferably 5 - 10 % Pd/C and the amount of catalyst used may is range from 5 - 100 % w/w. The reaction may also be caI-ried out by employing metal solvent reduction such as magnesium in alcohol or sodium amalgam irl alcohol, preferably methanol. The hydrogenation may be carried out in the presence of metal catalysts containing chiral ligands to obtain a compound of formula (I) iil optically active form. The metal catalyst may contain Rhodium, Ruthenium, hldiuln and the like. The chiral ligands may preferably be chiral phosphines such as optically pure enantiomers of 2,3-s bis(diphenylphosphino)butane, 1,2-bis(diphenylphosphino)ethane, 1,2-bis(2-methoxyphenyl phenylphosphino)ethane, 2,3-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino) butane and the lilce. Any suitable chiral catalyst may be employed which would give required optical purity of the product (I) (Ref : Principles of Asymmetric Synthesis, Tetrahedron Series ~lol 14, pp311-316, Ed. Baldwin J. E.).
Route 8 a The reaction of compound of formula (I~lb) where R4 is as defined earlier excluding hydrogen all other symbols are as defined earlier and L3 is a leaving group such as halogen atom with an alcohol of general formula (I~lc), ~s where R3 1S as defined earlier excluding hydrogen to produce a compound of the formula (I) defined earlier may be callied out in the presence of solvents such as THF, DMF, DMSO, DME and the like or mixW res thereof The reaction may be carried out ill an inert atmosphere which may be maintained by using inert gases such as N2, Ar, He and the like. The reaction may be 2o effected in the presence of a base such as KOH, NaOH, NaOMe, NaOEt, t-Bu0-I~+ or NaH or mixtures thereof Phase transfer catalysts such ~ as tetraallcylamlnonium halides or hydroxides may be employed. The reaction temperature may range from 20 oC - 120 oC, preferably at a temperature in the range of 30 oC - 100 oC. The diuatioiz of the reaction may range from 1 to 12 2s hours, preferably from 2 to 6 hours. The compound of general formula (IeJb) where R4 represents hydrogen or lower alkyl group and its preparation has been disclosed 11 Ollr US patent Nos. 5,885,997 and 5,985,884.

Route 9 : The reaction of compound of foninula (IIIg) defined earlier with compound of formula (TIIf) where all symbols are as defined earlier to produce a compound of the formula (I) defined above, may be carried out in the presence of solvents such as THF, DMF, DMSO, DME and the like or s mixtures thereof. The reaction may be carried Ollt 11 an snarl atmosphere which is maintained by using inert gases such as NZ, Ar, He and the like. The reaction may be effected in the presence of a base such as K2C03, Na2CO3 NaH and the lilce or mixtures thereof. Acetone may be used as' a solvent when K2C03 or Na2C03 is used as a base. The reaction temperature may range 1o from 20 oC - 120 oC, preferably at a temperature in the range of 30 oC - 80 oC. The duration of the reaction may range fr011n 1 to 24 hours, preferably from 2 to 12 hours. The compound of formula (IIIf) may be prepared by Wittig Horner reaction between the protected lnydroxyaryl aldehyde and compound of fonnula (IIIb) followed by reduction of the double bond and deprotection. Alternatively, the compowd of formula (IIIf) may be prepared by following a procedure disclosed in WO 94/01420.
Route 10 : The reaction of compound of general fonnula (IIIh) defined earlier with a compound of general formula (III where all symbols are as defined 2o above may be carried out using suitable coupling agents such as dicyclohexyl urea, triarylphosphineldiallcylazadicarboxylate such as PPh3 / DEAD and the like. The reaction may be canied out in the presence of solvents such as THF, DME, CHZC12, CHCl3, toluene, acetonitrile, carbon tetrachloride and the like.
The inert atmosphere may be maintained by using inert gases such as Na, Ar, 2s He and the lilce. The reaction may be effected in the presence of DMAP, HOBT and they may be used in tine range of 0.05 to 2 equivalents, preferably 0.25 to 1 equivalents. The reaction temperature may be in the range of 0 °C to 100 °C, preferably at a temperature in the range of 20 °C°to 80 °C. The duration of the reaction may range from 0.5 to 24 hours, preferably from 6 to 12 hours.
Route 11 : The reaction of compound of formula (IVd) which represents a s compound of formula (I) where all symbols are as defined above with a compound of formula (IVe) where R3 is as defined earlier excluding hydrogen and L3 is a halogen atom may be carried out ill the presence of solvents such as THF, DMF, DMSO, DME and the lilce. The inert atmosphere may be maintained by using inert gases such as NZ, Ar, He and the like. Tile reaction to may be effected in the presence of a base such as I~OH, NaOH, NaOMe, t-Bu0-K+,, NaH and the like. Phase transfer catalyst such as tetraallcylammonium halides or hydroxides may be employed. The reaction temperature may range from 20 oC to 150 oC, preferably at a temperature in the range of 30 oC to 100 oC: The duration of the reaction may range from 1 ~s to 24 hours, preferably from 2 to 6 hours.
The compound of formula (IVd) where R4 represents hydrogen or lower allcyl group and its preparation has been described in our IJS patent Nos.
5,885,997 and 5,985,884. The compound of formula (IVd) represents a compound of formula (I) where R~ represents hydrogen atolxl and all other 2o symbols are as defined earlier.
Route 12 : The reaction of a compound of the general formula (IIIa) as defined above with a compound of formula (IIIe) where R2 represents hydrogen atom and all other symbols are as defined earlier may be carried out under 2s conventional conditions. The base is not critical. Any base normally employed for aldol condensation reaction may be employed, metal hydride such as NaH
or Iii; metal alleoxides such as NaOMe, t-BuOT~t or NaOEt; metal amides such as LiNH2, LiN(iPr)Z. Aprotic solvent such as THF may be used. Inert atmosphere may be employed such as argon and the reaction is more effective under anhydrous conditions. Temperature ill the range of -SO °C to 25 °C may be used. The ~3-hyclioxy aldol product relay be dehydroxylated using conventional methods, conveniently by ionic hydrogenation technique such as by treating with a triallcyl silane in the presence of an acid such as s trifluoroacetic acid. Solvent such as CHZC12 may be used. Favorably, reaction proceeds at 25 °C. Higher temperattue may be employed if the reaction is slow.
Route 13 : The reaction of a compound of general formula (IIIc) where all symbols are as defined earlier with a compound of general formula (IIId) where I,1 is a leaving group such as halogen atom, p-toluenesulfonate, methanesulfonate, trifluon omethanesulfonate and the life, pz eferably a halogen atom and all other symbols are as defined earlier to produce a compound of general formula (I) where all symbols are as defined above may be carried out is in the presence of solvents such as DMSO, DMF, DME, THF, dioxane, ether and the like or a combination thereof. The reaction lnay be carried out in an inert atmosphere which 'may be maintained by using inert gases such as IV2, Ar, He and the like. The reaction may be effected in the presence of a base such as alkalis like sodium hydroxide, potassilun hydroxide; alkali metal 2o carbonates lilee sodium carbonate or potassium carbonate; alkali metal hydrides such as 50d111111 hydride or potassium hydride; organometallic bases lilce n-butyl lithium; alkali metal amides like sodamide ox mixtures thereof The amount of base may range from 1 to 5 equivalents, based on tile am~unt of the compound of fol-mula (IIIc), preferably the alnolmt of base ranges from 2s 1 to 3 equivalents. Additives such as alkali metal halides such as IJiBr may be added. The reaction may be carried out at a temperature in the range of 0 oC
to 150 oC, preferably at a temperature in the range of 15 oC to 100 oC. The duration of the reaction may range fr01110.25 to 48 hours, preferably from 0.25 to 24 hours.

Route 14. : The conversion of compound of fomula (IVf) where all symbols are as defined earlier to a compound of formula (I) may be carried out either in the presence of base or acid and the selection of base or acid is not critical.
~ Any base normally used for hydrolysis of nitrite to acid may be employed, metal hydroxides such as NaOH or KOH in an aqueous solvent or any acid normally used for hydrolysis of nitrite to ester niay be employed such as dry HCl in an excess of alcohol such as methanol, ethanol, propanol ~ etc. The reaction may be carried out at. a temperature in the range of 0 ~°C to reflux to temperature of the solvent used, preferably at a temperature in the range of 25 °C to reflux temperature of the solvent used. The duration of the reaction may range from 0.25 to 48 hr s Route 15 : The reaction of a compound of formula (IVg) where R4 is as is , defined earlier excludiilg hydrogen and all symbols are as defined earlier with a compound of formula (IVc) where R3 is as defined earlier excluding hydrogen to produce a compound of fornula (I) (by a rhodium carbenoid mediated insertion reactibn) may be carried out in the presence of rhodium (II) salts such as rhodium (II) acetate. The reaction may be carried out in the 2o presence of solvents such as benzene, toluene, dioxane, ether, THF and the like or a combination then eof or when practicable in the presence of R6OH as solvent at any temperature providing a convenient rate of formation of the required product, generally at an elevated temperature, ~ such as reflux temperature of the solvent. The inert atmosphere may be maintained by using 25 inert gases such as NZ, Ar, He and the like. The duration of the reaction may be range from 0.5 to 24 h, preferably from 0.5 to 6 h.
The compound of general fornula (I) where R4 represents hydrogen atom may be prepared by hydrolysing using conventional methods, a compound of formula (I) where R4 represents all groups defined earlier except hydrogen. The hydrolysis maybe carried out in the presence of a base such as Na2CO3 and a suitable solvent such as methanol, ethanol, water and the like or mixtures thereof. The reaction may be carried out at a temperature in the range s of 20-120 °C, preferably at 25-30 °C. The reaction time may range from 2 to 48 h, preferably from 4 to 12 h.
The compoLmd of general fomnula (I) where Y represents oxygen and R4 is as defined earlier may be converted to compound of formula (I), where Y
represents NRS by reaction with appropriate amines. Suitably the compound of to formula (I) where YR4 represents OH may be converted to ~ acid halide, preferably YR4 = halogen, by reactiizg with appropriate reagents such as oxalyl chloride, thionyl chloride and the like, followed by treatment with amines;
Alten~atively, mixed aWydrides may be prepared from compound of formula (I) where YR4 represents OH and all other symbols are as defined earlier. by is treating with acid halides such acetyl chloride, acetyl bromide, pivaloyl chloride, dichlorobenzoyl chloride and the like.' The reaction may be carried out in the presence of suitable base such as pyridine, triethylamine, diisopropyl ethylamine and the like. Solvents such as halogenated hydrocarbons lilce CHCl3, CHZC12, hydrocarbons such as benzene, toluene, 2o xylene and the lilce may be used. The reaction may b'e carried out at a temperature in the range of -40 °C to 40 °C, preferably 0 °C to 20 °C. The acid halide or mixed anhydride thus prepared may furthex be treated with appropriate amines.
25 In another embodiment of the present invention there is provided the novel intermediates of formula (IVf) R~
R~
A-(CH2)~-O-Ar CN (IVf~

where R1 represents hydrogen-atom, halogen, hydroxy, lower alkyl, alkoxy, substituted or unsubstitiited aralkyl group or fours a bond together with the adjacent group R2; RZ represents hydrogen, hydroxy, halogen, lower alkyl, alkoxy, allcanoyl, amyl, aralkanoyl, substiW ted or Lulsubstituted aralkyl or R2.
s forms a bond together with Rl; R3 array be hydrogen atorn or substituted ° or unsubstituted groups selected from alkyl, cycloallcyl, ar~rl, allcanoyl, aroyl, . arallcyl, heterocyclyl, heteroaryl, heteroarallcyl, ~allcoxyallcyl, alkoxycarbonyl, aryloxycarbonyl, allcylaminocarbonyl, arylaminocarbonyl groups, n is an integer ranging from 1- 4; Ar represents substiW ted or unsubstituted, divalent9 single or fused, aromatic or heterocyclic group; A represents a cyclic structure given below a X X X ' X
\ \

R7 N . ° I N R7 S I N R' O ~ N ~ I N
$ N~R6 ~'R$ N~R6 ~'R$ N~R6 °R$ ~ N~R6 X X X ~ X
R7~N ~ N R7, N ~ N R~ ~ N 1~7~~ N
N~ ~~ 6 Rg~~ (~~~ 6 8 S~ ~, 6. g ~~ ~g 6 N R R R (~ R R N R
X . X X X
_N R7 N ( N R7' ~ N R7< N I N
' ' B 0 _ ~ _ ~ _ ~,6 S '~~6 O N~'6 R$~N ~g6 R N R N R R N R
X X X X X
R7WS ~ N R7\N N Ry0 N R7~N~ N RyN~ N
_' _' ~\ ~ ~ o ' S~.~ a 'N I NxRs R$ N I N~Rs N NXFt6 R8 ~ N~~s R$ N~R6 where X represents O or S; R~ when attached to the carbon atom represents hydrogen, halogen, hydroxy, vitro, cyano, fomnyl or substituted or unsubstituted groups selected from allcyl, cycloallcyl, allcoxy, ~cycloallcoxy, aryl, aryloxy, arallryl, arallcoxy, heterocyclyl, heteroalyl,, heteroaralkyl, heteroaryloxy, heteroarallcoxy, allcanoyl, aroyl, allcanoyloxy, hydroxyalkyl, amino, acylamino, monoallcylamino, diallcylamino, arylamino, aralkylamino, s aminoalkyl, alkoxycarbonyl, aryloxycarbonyl,, arallcoxycarbonyl, alkoxyalkyl, aryloxyallcyl, arallcoxyallcyl, alleylthio, thioallcyl, alkoxycarb~nylamirlo, . aryloxycarbonylamino, arallcoxycarbonylamino, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R~ when attached to nitrogelx atom represents hydrogen, hydroxy, formyl or substituted ox unsubstituted groups selected from alkyl, cycloallcyl, alkoxy, cycloalkoxy, aryl, arallcyl, aryloxy, arallcoxy, heterocyclyl, heteroaryl, heteroarallcyl, heteroaryloxy, heteroarallcoxy, allcanoyl, , amyl, allcanoyloxy, hydroxyallcyl, amino, monoallcylamino, diallcylalnino, alylamino, arallcylamino, amirloalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, ~s aryloxyalleyl, aralkoxyallcyl, allcylthio, thioallcyl groups, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R' and R8 when attached to carbon atom may be same or different and represent hydrogen, halogen, hydroxy, cyano, vitro, forlnyl or substituted or unsubstituted groups selected from alkyl, allcoxy, aryl, aryloxy, arallcyl, arallcoxy, heterocyclyl, heteroaryl, 2o heteroarallcyl, hydroxyalkyl, a1111110, 1110110alkylamm~, dialkylamino, arylalnino, arallcylamino, alninoallcyl, allcoxyallcyl, tb ioallcyl, allcylthio groups;
R7 and R8 when attached to nitrogen may be same or different and represent hydrogen, hydroxy or substihited or unsubstiW ted groups selected from alkyl, allcoxy, aryl, aryloxy, ar alkyl, ar allcoxy, heterocyclyl, peter oaryl, heteroaralkyl, 2s hydroxyallcyl, amino, 111o110al1Cyla111ll10, diallcylalnino, arylamino groups and a process for its preparation and its use in the preparation of (3-axyl-a,-oxysubstituted allcylcarboxylic acids is provided (Scheme-III).

A-(CHI),; O-Ar-CHO
Base (Illa) ø A-(CH2)n'O-Ar-CH=CH-ORS
(I\/1) R30CHZP''Ph3 Hal (IVh) R6OH
R' z A-(CH2)n'O-Ar~CN ~ A-(CHZ)n'O-Ar JJR\ R'2 R3O~'- 3~OR3 RO
(I~~
(I~l) Scheme III
. The reaction of a C0111pOlllld of formula (IIIa) where all symbols axe as s defined earlier with a compomd of formula (IVh) where R3 is as defined ea~'liex excluding hydrogen and Hal represent a halogen atom such as Cl, Er, I
to produce a compound of formula (IVi) where all symbols are defined earlier and R3 is as defined earlier excluding hydrogen may be carried out border conventional conditions in the presence of a base. The base is not critical.
Any ~o , base normally employed for Wittig reaction may be employed, metal hydride such as NaH, I~H, metal allcoxides such as NaQMe, I~tEu~-, Na~Et, metal amides such as LiNH2, LiN(iPr)2. Aprotic solvent such as THP, 1JMS~, dioxane, DME and the life may be used. Mixture of solvents may be used.
HMPA may be used as cosolvent. Inert atmosphere may be employed such as~
Is argon and the reaction is more effective under anhydrous conditions.
Temperature in the range of -80 °C to 100 °C may be used.
The compound Of f01111111a (IVi) where all symbols are as defined earlier and R3 is as defined earlier excluduzg hydrogen rnay be converted to a compound of formula (IVj) where all symbols are as defined earlier,' by 2o treating with an alcohol under anhydrous conditions iiz the presence of a strong anhydrous acid such as ~-toluenesulfonic acid.

The compound of foriiiula (IVj)' defiized above upon treatment with .:
' trialkylsilyl cyanide such as tri'rnethylsilyl cyanide produces a compoW d of formula (IVf) where all symbols are as defined earlier.
s In still another embodiment of the present invention there is provided the novel interrriediates of formula (IVg) ' , ' R~ .
p A-(CH2)n'C'/~r~,OR4 (IVg) NjZ~
where Rl represents hydrogen atom; halogen, hydroxy, lovc~er alkyl, alkoxy, substituted or urisubstituted aralkyl group; R4 may be hydrogen or substituted or urisubstituted groups selected from alkyl, cyclo~.lkyl, aryl, aralkyl, heterocyclyl, heteroaryl or heteroaralkyl groups; n is' am integer ranging fromi 1- 4Ar represents substituted or unsubstitiited, divalent, single or fused, aromatic or heterocyclic group; A represents a cyclic structure given below X X X . X
7 N N 7 5 N p . N RAN N
R ~ ~ ~ R ~ ~ ~~: R7 ~ ~ ~ 6 8~ I ~C 6 Ra N R6 Rs N R6 Rs N R R N R
X X. X X
R7\N\ N R7~N' N ° R7\~ N R7\~ N
~C' $~ ~ ~C' N N Rs R N R R S N R6 R N N R6 X Xy .X X
R7 ~ N R7 N N. R7 N N R7 N N
<i ~ ~ x~ ~ ~ ~~ , ' . I ~~
R$ O N Rs S N Rs O N R6 R N N Rs X X X X X
p N R7~N' N R~~N~ N
N NxRs R$ N N~Rs N N Rs R8 . N~Rs Rs N Rs where X represents O or S; R6 W hen attached to the carbon atone represents hydrogen, halogen, hydroxy, vitro, cyano, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, s aryl, aryloxy, aralkyl, aralkoxy, hetefocyclyl, heteroaryl, lieteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, amyl, alkanoyloxy; hydroxyalkyl;
amino, acylamino, monoalkylamino, dialkylamino, arylamino, aralkylainino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, ' aryloxyalkyl, aralkoxyalkyl, allcylthio, thioalkyl, alkoXycarbonylamin~, to aryloXycarbonylamino, arallco~cycarbonylarriiri'o, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R6 when attached to nitrogen atom represents hydrogen, hydroa~y, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloallcoxy, aryl; aralkyl, arylo~y, aralkoxy, heterocyclyl, heteroaryl, heteroaialkyl, lieteroaryloxy, is heteroaralkoxy, alkanoyl, aroyl, allcanoyloxy, hydroxyalkyl, aW ino, Tnonoalkylamino, dialkylamino, arylamino, aralkylamino, " arilinoalkyl, allcoxycarbonyl, aryloxycarbonyl, aralkoxycarb'oriyl, alkoxyalkyl, aryloxyalkyl, aralkoXyalkyl, allcylthio, thioalkyl groups, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R7 and R8 when attached to 2o carbon atom may be same or different and represent hydrogen, halogen, hydroxy, cyano, vitro, formyl or substituted or unsubstituted groups selected from allcyl, allcoXy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyallsyl,, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxyalkyl; thioalkyl, alkylthio groups;
2s R' and R8 when attached to nitrogen W ay be same or different and represent hydrogen, hydroxy or substituted or unsubstituted groups selected from alkyl, allcoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyall~yl, amino, monoalkylamino, dialkylamino, arylamino groups and a process for its preparation and its use in the preparation of (3-aryl-oc-oxysubstituted alkylcarboxylic acids is provided.
The compound of formula (IVg) where all other symbols are as defined earlier may be prepared by reacting a compound of formula (IVk) R~
Rz O
A-(CH~)~ O-Ar OR4 (IVk) s H2N
where RZ , is hydrogen atom and all other symbols are as defined earlier, with an appropriate diazotizing agent.
Tlie diazotization reactioil iizay be W der conventional conditions..A
suitable diazotizing agent is an alkyl nitrile~ such as' iso-amyl nitrite. The reaction 'may be carried out in presence of solvents such ~s THF, dioxane, ether, benzene and the like or a combination thereof. Temperature in the range of -50 °C to 80 °C may be used. The reaction may be carried out in an inert atmosphere which may be maintained by using inert gases such as Nz, Ar or is He. The duration of the reaction may range from 1 to 24 h~ preferably, 1 to h.
The compound of formula (IVk) may also be prepared by a reaction between (IIIh) where all syrilbols are as defined earlier and a compound .of 20 formula (IVl) HO-Ar~OR4 (1V1) HZN
where Ra is hydrogen atom and all other symbols are as defined earlier.
The reaction of compound of formula (IIIh) where all syriibols are as defined earlier and a compound of formula (IVl) where all symbols are as 2s defined earlier may be carried out in the presence of solvents such as THF, DMF, DMSO, DME and the like or mixtures thereof. The reaction may be carried out in an inert atmosphere which is ruaintained by using inert gases such as N2, Ar or He. The reaction niay be effected in the presence of a base such as K2C03, Na2C03 or NaH or mixtures thereof. Acetone inay be used as a. solvent when K2CO3 or Na2C03 is used as a base. The reaction s temperature may range from 20 oC - 120 oC, preferably at a temperature in the range of 30 oC - 80 oG. The duration of the reaction may range from 1 to 24 hours, preferably from 2 to 12 hours.
It is appreciated that iiy any of the above mentioned reactions, any reactive group iii the substrate molecule may be protected according to io conventional chew ical practice. Suitable protecting groups iri any of the above mentioned reactions are those used conventionally in the art. The methods 'of formation and removal of such protecting groups are those conventional methods appropriate to the molecule being protected:
is The pharmaceutically acceptable salts are .prepared by reacting the compounds of formula (I) wherever applicable with 1 to 4 equivalents of a base such as sodium hydroxide, sodium methoxide, sodium hydride, potassium t-butoxide, calcium hydroxide, magnesium hydroxide and the like, in solvents like ether, THF, methanol, t-butamol, dioXane, isopropauo~l, ethanol 2o etc. Mixture of solvents may be used. Organic bases like lysine, arginine, diethanolamine, choline, trometharuine, guanidine and their derivatives etc.
may also be used. Alternatively, acid addition salts wherever applicable are prepared by treatment with acids such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric ~ acid, p-toluenesulphonic acid, 2s methanesulfonic acid, acetic acid, citric acid, malefic acid salicylic acid, hydroxynaphthoic acid, ascorbic acid, palmitic acid, succinic acid, benzoic acid, benzenesulfonic acid, tartaric acid and the like in solvents like ethyl acetate, ether, alcohols, acetone, THF, dioxane etc. Mixture 'of solvents may also be used.

The stereoisomers of the compounds forming part of this invention may be prepared by using reactants in their single enantibmeric form in the process wherever possible or by conducting the reaction in the presence of reagents or catalysts in their single enantionier form or by resolving the mixture of s stereoisomers by conventional methods. Soriie of the preferred methods include use of microbial resolution, resolving the diastereoriieric salts for :red with chiral acids such as mandelic acid, camph'orsulfonic acid, tartaric acid, lactic acid, and the like wherever applicable or chiral bases such as brucine, cinchona alkaloids and their derivatives and the like. Commonly used methods 10 are compiled by Jaques et al in "Enantiomers, Raceinates and Resolution"
(Wiley Interscience, 1981). More specifically the compound of formula (I) ' where YR4 represents OH may b'e converted to a 1:1 mixture of diastereomeric ' amides by treating with chiral amines, aminoacids, arninoalcohols derived from aminoacids; conventional reaction conditions may be employed to is convert acid into an amide; the. diastereomers may be separated either by fractional crystallization or chromatography ._e.and the stereoisomers." of compound of formula (1) may be prepared by Hydrolyzing the . pure diastereomeric amide.
Various polymorphs of compounds of general formula (I) and (IIIm) 20 , 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 crystallization; crystallizations at different temperatures; various modes of cooling, ranging from very fast ~to very slow cooling during crystallizations. Polymorphs may also be obtained ' 2s 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 also provides a pharmaceutical composition, containing the compounds of the general formula (I) as defined above, their derivatives, their analogs, their tautoriler'ic forms, their stereoisomiers, their polymorphs, their pharniaceutically acceptable salts, their , pharmaceutically s acceptable solvates in combination with the usual pharmaceutically employed carriers, diluents and the like, useful for the treafxnent and / or prophylaxis diseases such as hypertension, coronary heart disease, atherosclerosis, stroke, peripheral vascular diseases and related disorders. These compounds are useful for the treatment . of familial hypercholesteroleW ia;
1o hypertriglyceridemia, lowering of atlierogeriic lipoproteins,. 'VLIDL and LDL.
The coW pounds of the present invention can be used for the treatment of certain renal diseases including glomerul'onephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis, retinopathy, nephropathy.
The compounds of general formula (I) are also useful for the treatment /
is prophylaxis of insulin resistance (type II diabetes), leptin resistance, impaired glucose tolerance, dyslipidemia, disorders related' to syndrome X such as hypertension,. obesity, insulin resistance, coronary heart disease, and other cardiovascular disorders. These compounds may also be useful as aldose reductase inhibitors, for improving cognitive functions in dementia, treatW g 2o diabetic complications, disorders related to endothelial cell activation, psoriasis, polycystic ovarian syndrome (PCOS), inflaiizmatory boW e1 diseases, osteoporosis, myotonic dystrophy, pancreatitis, arteriosclerosis, Xanthoma and for the treatment of cancer. The compounds of the present inventions are useful in the treatment and l or prophylaxis of the above said diseases in 25 combination / concomittant with one or more H1VIG CoA reductase inhibitors, hypolipiderizic / hypolipoproteinemic agents such as fibric acid derivatives, nicotinic acid, cholestyramine, colestipol, probucol. The compounds of , the present invention in combination with HMG CoA reductase ~ inhibitors, hypolipidemic / hypolipoproteineniic agents can be administered together or within such a period to act synergistically. The HMG CoA reductase inhibitors may be selected from those used for the treatment or prevention .of hyperlipidemia such as lovastatin, provastatin,. 'simvastatin; fluvastatin, atorvastatin, cerivastatin and their analogs thereof. Suitable filiric acid derivative may be gemfibrozil, clofibrate, fenofbrate, ciprofibrate, benzafibrate and their analogs thereof, The pharmaceutical corriposition may be in the forms normally employed, such as tablets, capsules, powder's, syrups, solutions; suspensions and the like, may contain flavourant's, sweeteners etc. in 'suitable solid or 1o liquid carriers or diluents, or in suitable sterile media to foim inj~ectable solutions or suspensions. Such com'positioris typically contain froriz 1 to 20 %, preferably 1 to 10 % by weight of active compound, the rerilainder of the corriposition being pharmaceutically acceptable carriefs~ diluents or solvents.
The compound of the formula (I) as defnled above are clinically administered to mammals; including man, via either oral or parerlteral routes.
Administration by the oral route is preferred being more 'coriVenient arid avoiding the possible pain and irritation of injection. however, in circumstances where the patient caxmot swallow the medication or absorption following oral administration is unpaired, as by disease ~or other abnormality, 2o it is essential that the drug be administered parenterally. By either route, the dosage is in the range of about 0.01 to about 100 riig / kg body weight of the subject per day or preferably about 0.01 to about 30 irig / kg body weight per day administered singly or as a divided dose. However, the optimum dosage for the individual subject being treated will be determined by the person responsible for treatment, generally smaller doses being administered initially and thereafter increments made to determine the most suitable dosage.
Suitable pharmaceutically acceptable carriers include solid fillers or diluents and sterile aqueous or organic solutions: The active compound will be present in such pharmaceutical compositions in the amounts sufficient to provide the desired dosage in the range as described above. Thus, for oral administration, the compounds can be combined with a suitable sofiid or liquid carrier or diluent to form capsules, tablets, powdersa syrups, solutions, suspensions and the like. The pharmaceutical compositions, may, if desired, contain additional c'omponerits such as flavourants; sweeteners, excip'ients and the like: For ,parenteral administration, the compounds can b'e combined with sterile aqueous or organic media to form injectable solution's or suspensions.
For example, solutions in sesame or peanut oil, aqueous propylene glycol and the like can be used, as well as aqueous solutions of water-soluble pharmaceutically acceptable acid addition salts or salts with 'base of the compounds. The injeetable solutions prepared in this manner can there be administered intravenously, intraperitoneally; subcutaneously, or intramuscularly, with intramuscular administratibn being preferred in humans.
The invention is explained in detail in the examples given below which are provided by way of illustration oril~ and therefore should not be construed to limit the scope of the invention.
Preparation 1 ao Ethy12,4-dioxoheptanoate ~ o C02Et Sodium (11.5 g, 500 mmol) was added to ethanol (130 mL) in portions at room temperature with vigorous stirring. After sodium got dissolved, the solution was cooled to 0 °C. Methyl propyl ketone (53.0 ml,, 500 mmol) was added dropwise and the stirring was continued for further 15 - 20 min. Diethyl oxalate (68.0 mL, 500 mmol) was added dropwise to the resulting solution at 0 °C and the stirring was continued for another 15 min at 0 °C.
The reaction mixture was .then allowed to attain room temperature and the stirring was s4 continued for further 12 h at this teW perature. '~'he reaction mixture was then kept in refrigerator for 24 h. The solvent was removed W der vacuuiiz at room temperature. The resulting residue was diluted with dil. hydrochloric acid on an ice.bath arid extracted the aqueous layer with diethyl ether (4 x 50 mL).
The s combined ether extracts were washed with water, brine, dried (Na2S04) and concentrated under vacuum. The crude mass was chromatographed ~n silica gel using 3 % ethyl acetate in pet. ether as eluerit to yield the title compound (60.0 g, 64.5 %).
1H N1VIR (CDCl3) : 8 14.45 (broad s, D20 excharigeablea 1H); 6.33 (s, 1~i), 4.32 (q; J = 7.10 Hz, 2H), 2.44 (t, J = 7.40 Hz, 2H), 1.72 - 1.57 (m, 2I~), 1.35 (t, J = 7.30 Hz, 3H), 0.94 (t, J = 7.40 Hz, 3H).
Preparation 2 .
Ethyl 3-propyl-1H-5-pyrazole carboXylate (2A) .
is 3-Propyl-1H-5-pyrazole carboxylic acid (2B) HN-N HN=N
\ \..
Et02C ~ HOOC

To a stirred miXture of ethyl 2,4-dioxoheptanoate (28.0 g; 150 miizol) obtained in preparation l, acetic acid (225 mL) and methoxy ethanol (225 mL);
hydrazine hydrochloride (31.6 g, 300 mmol) vas added and heated to 105 °C
2o for 3 h. Acetic acid and methoxy ethanol were removed under vacuum at 90 °C. The residue was talcen in water and extracted three times with ethyl acetate. The combined organic layers were washed with vsiater, brine, dried (Na2S04) and concentrated to obtain solids suspended in liquid: Th'e solids , were filtered and washed pith pet. ether to yield the title compound 2B (5.0 g, 2s 21.6 %). The solvent was evaporated from the filtrate to yield 2A (16.0 g, 58.4 %) as liquid.

ss 2A 1H NMR (2A) (CDC13) : ~ 6.57 (s, 1H), 4.34 (q, J = 7.10 Hz, 2H), 2.65 (t, J
7.50 Hz, 2H), 1.71-1.59 (rim, 2H), 1.33 (t, J = 7.20 Hz, 3H), 0.92 (t, J =
7.30 Hz, 3H).
s Preparation 3 1-Methyl-3-propyl-1~3f-5-pyrazole'carboXyli'c acid Me N-N~ , COOH
Dimethyl sulfate (6.0 g, 48.35 mnlol) was added to the pyrazole ester obtained in preparation 2 (1'6.0 g, 88 mmol) and the reaction mixtuie vcias heated at no °C for 2 h. The reaction mixture was cooled to ~ 90 °'C and SN sodiurri hydroxide, solution (64 mL) was added and the reaction ini~ture was stirred at 80 - 90 °C for 30 min. The reaction mixture was cooled in an ice bath and was acidified to pH 4 with 2N hydrochloric acid resulting precipitation of the product. The precipitate was filtered, washed with cold water and dried under 1 s vacuum to yield the title compound ( 12.0 g, 81 %).
1H NMR (CDCl3) : 8 6.70 (s, 1H), 4.14 (s, 3H), 2.64 (t, J = 760 Hz; 2H), 1.72 -1.61 (m, 2H), 0.95 (t, J = 7:30 Hz, 3H).
Preparation 4 20 1-Methyl-4-vitro=3-propel-1~I-5-pyrazole carboXylic acid 1 Me ' N-N
~ a , COOH
N 02 .
Nitrating agent was prepared by adding 90 % nitric acid (7.18 mL) to concentrated sulphuric acid (13.8 mL) at 75-78 °C. 1-Methyl-3-propyl-1H-pyrazole carboxylic acid (11.5 g, 68.4 minol) obtained in preparation 3, was 2s added to the nitrating agent portion wise with stirring so that the temperature is maintained at ~ 85 °C. After the complete additi~n, the mixture was heated at 100 °C for 2 h. The reaction mixture was cooled and poured into crushed ice. The suspension was filtered cold (10 °C) and the solids Were washed with ice cold brine and dried to yield the title compound (5.0 g; 34 %).
s ,1H IV1VIR (CDCl3) : 8 6.90 (broad s, DSO exchangeable, 1H), 4:20 (s, 3H), 2.90 (t, J = 7.60 Hz, 2H), 1.'79-1.64 (m, 2H), 1.02 (t, J = 7.40 Hz, 3I~).
Preparation 5 3.-Methyl-4-vitro-3-propyl-1H-5-pyrazole carboxamide Me .
N_N' ,/ ~

1p N~2 Thionyl chloride (7.2 mL, 98 mmol) was added to 1 _methyl-4-vitro-3-propyl-1H-5-pyrazole carboxylic acid obtained in preparation 4 (3.3 'g, 15.5 mrizol) and refluxed for 3.5 h. The excess thionyl chloride was removed from the reaction .mixture under vacuum and the residue vas taken iri dry acetone (20 ~s mL). AW monia gas was passed through this solution till pH reached 8=9. The precipitate formed was filtered. The filtrate was' concentrated and then' dissolved in ethyl acetate. The organic phase wa's washed with water, brine, dried (Na2S04) and concentrated to yield the title; compound a's a fluffy material (3.1 g, 94 %).
20 1H NMR (CDC13) : 8 7.50 (broad s, D20 exchangeable; 1H), 6.08 (broad s, D20 exchangeable, 1H), 4.05 (s; 3H), 2.86 (t, J = 7.70 Hz, 2H), 1.75-1.60 (m, 2H); 0.98 (t, J = 7.30 Hz, 3H).
Preparation 6 2s 4-Amino-1-methyl-3-propyl-1H-5-pyrazole carb'oxamid'e s7 Me w N_N' CONH2 , To a solution of 1-methyl-4-vitro-3-propyl-1H-5-pyrazole carboxamide obtained in preparation 5 (3.2 g, 15.0 riunol) in methanol (30 rinL), IZaney nickel (450 mg) was added and hydrogenated b'y passing hydrogen gas at 50 s psi for 10 h. The reaction mixture was filtered through celite bed and washed with methanol. The filtrate arid washings were combined, concentrated, purifed by silica gel colurizn chromatography using ethyl acetate-pet. ether (1 1) a's eluent to yield the title compound (2:0 g., 73 %).
1H NMR (CIDC13) : 8 7.05 (broad s, D20 exchangeable, 2Ji), 4.07 (s; 3H), 2.75 to (broad s, D20 exchangeable, 2H), 2.51 (t, J = 7.60 Hz, 2H); 1.69 = I.50 (rim, 2H), 0.95 (t, J = 7.30 Hz, 3H).
Preparation 7 . , 5-Ethyl-1-methyl-3-propyl-6,7-dihydro-1H-pyrazolo[4;3-d]pyrimidin-7-is one p N NH.
N .L
~ N
~'~ 4-amino-1-riiethyl-3-propyl-1H-5-pyrazole carboXaW ide obtained. in preparation 6 (1:3 g, 7.1 mmol) in xylene (10.5 mL), propidnic acid (10.5 iii,) was added and cooled in ice bath. Triethyl amine (2.2 ml,; 15.7 mniol) was 20 added to the reaction mixture and stirred for 15 ruin. Propionyl chloride was added and stirred at the same , temperature for 30 min. The reaction mixture was refluxed for 36 h and the solvent was removed under vacuum. The resulting residue was diluted with water and extracted with ethyl acetate (3 X
mlL). The combined organic extracts were vc~ashed with water, brine, dried 2s (Na2SO4) and concentrated. The crude compound wa's purified by silica gel s8 column chromatography using 30 % ethyl acetate iri pet: ether as eluent to yield the title corripound (560 mg; 36 %).
1H NMR (CD'C13) : ~ l 1.1 (broad s, Da0 exchangeable, 1H), 4.23 (s, 3H), 2.89 - 2.69 (m, 4H), 1.85 -1.71 (m, 2H), 1.37 (t, J = 7.50 Hz, 3H), 0.98 (t, J =
7.40 s Hz,.3H).
Preparation 8 1,5-Dimethyl-3-propyl-6,7-dihydro-1H-pyr~zolo[4,3-d]pyririiidin-7-one N , sNH
N~
to The title compound (360 mg, 36 %) was obtained as fluffy solid from 4-amino-1-methyl-3-propyl-1H-5-pyrazole carboxamide (950 mg, 5.2 mmol) obtained in preparation 6, acetyl chloride (450 mg, 5.74 iiiiriol); triethyl arriine (1.15 g, 11.48 mrriol) and acetic acid (7.5 mL) by refluXing in xylerle (7.5 inL,) for 72 h following a similar procedure as described in preparation 7.
~s 1H NMR (CI~C13) : b 11.18 (broad s, D20 eXChangeable~ 1H), 4.23 (s; 3I~), 2.84 (t, J = 7.60 Hz, 2H), 2.51 (s, 3H), 1.84 =1.75 (m, 2H), 0.9'8 (t, J =
7.30 Hz, 3H).
Preparation 9 20 1-Methyl-3-propyl-5-trifluoromethyl=6,7-dihyd'ro-1H-pyrazolo [4,3-d]pyrimidin-7-one N~CF3 N/ I . NH
N' The title compound (275 mg, 96.2 %) vvas obtained as fluffy ,solid from 4-amirio-1-methyl-3-propyl-1H-5-pyrazole carboXamide - (200 riig, 1.09 mmol) obtained in preparation 6; trifluoroacetic arihydrid'e (0.17 rn~, '1.2 mmol) and propionic acid (2.5 mL) by refluxing in xylene (2.5 ml,) for 24 h following a similar procedure as described in preparation 7, mp 1985 - 200.5 °C.
1H NMR (CDCl3) :. 8 11.40 (broad s, I~20 exchangeable, 1H), 4.29 (s, 3H), s 2.91 (t, J = 7.60 Hz, 2H)~ 1.92 =1.72 (ril; 2I3); 1.00 (t; J = 7.30 Hz, 3H).
Preparation 10 5-Benzyl-1-methyl-3-propyl-6,7-dihydro-lI3-pyrazolo [4,3-d]pyrimidiri-7-one 'J'he title compound (115 mg, 37 %) was obtained as a fluffy solid from 4-amino-1-methyl-3-propyl=1H-5-pyrazole carboxarizide (200 mg, 1.09 W mol) obtained in preparation 6, phenylacetyl chloride (0.159 mI:; 1.2 mrizol)-triethylamine (0.336 mL, 2.40 W rriol) and propioriic acid (2.5 rriL) by is refluacing in xylene (2.5 mL) fox 36 h following a similar procedure .as described in preparation 7, mp 174-179 °C.
1H N1~R (CDCl3) : 8 7.32 - 7.26 (m, SH), 4.21 (s, 3gi), 4.04 (s; 2II); 2.89 (t, J
= 7.5.0 I-Iz; 2H), 1.9'0 -1.75 (rim, 2H), 1.02 (t, J = ?.3'O Hz, 3H).
20 Preparation 11 3,5-Dipropyl-1-methyl-6,7-dihydro-1H-pyrazolo [4,3-d] pyrimidin-7-one N\~
N
N
N
N.~ I ~~ '' ,N ~H ..
The title compound (550 mg, 71.3 %) was obtained as a fluffy solid from ,4-amino-1-riiethyl-3-propyl-1H-5-pyrazole carboxamide (600 mg, 3.3 mmol) .

obtained in preparation 6, butyryl chloride (0.38 W L, 3.62 mmol), triethyl amine ( 1 mL, 7.25 mmol) and propionic acid (4 iiiL) by refluxing in xylene (4 mL) for 48 h following a similar procedure as described in preparation 7, mp 180-182 °C.
s 1H NMR (CDC13) : b 11.00 (broad s, D20 exchangeable, 1H), 4.22 (s, 3H), 2.84 (t~ = 7.60 Hz, 2H), 2.68 (t, J = 7.80 ~iz9 2H), 1.92 =1.65 (m, 4H), 1.01 (t, J = 7.20 Hz, 3H), 0.97 (ta J = 7.30 Hz~ 3I~).
Example 1 io Ethyl 2-ethoxY-3-[4-[2-(5=ethyl-1-methyl-7-oxo-3-propyl-6;7-dihydro-1Hf-pYrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoate ~ I ,N ~ ~ I oEt N'N~ N~~ \ OED
A mixture . of 5-ethyl-1-rizethyl-3-propyl-6,7-diliyd'ro-1H-pyrazolo[4,3 is d]pyrimidin-7-one (100 nig, 0.454 ~iW o1) obtained in preparation 7 and anhydrous K2C03 (188 nig, 1.36 mmol) in dry N,N diriiethylformariiide ~(2 mL) was stirred under argon atmosphere for 30 min at room teW peratuie.
Ethyl 3-[4-(2-bromoethoxy)phenyl]-2-ethoxyp_ropanoate (188 mg, 0.545 mmo~l) prepared as disclosed in US patent application 09/012,585 taken in dry 2o N,N dimethylforrilamide (2 mL) was added. The reaction ini~ture Was stirred at room temperature for , 8 h~ diluted with water and extracted with ethyl acetate (3 X 10 rnL). The combined organic extracts were ~ivashed With water, brine, dried (Na2S0~) and evaporated to dryness. The title compound (150 mg, 68 %) was obtained by purifying over silica gel column using 20 % ethyl 25 acetate in pet. ether as eluent, mp 112 °C.

1~I NMR (CDC13) : ~ 7.10 (d, J = 8.60 Hz, 2H), 6.76 (d, J = g.40 ~Iz, 2H), 4.49 (t, J = 5.20 Hz, 2H), 4.29 - 4.10 (ni,~ 7H), 3.93 (t, J = ~ 7.00 IIz, 1H), 3.65 -3.20 (m,.2H), 3.09 - 2.81 (m, 6H), 1.93 - 1.75 (in, 2H), 1.38 (t, J = 7.30 Hz9 3H), 1.26 -1.11 (m, 6H), 0.99 (t, J = 7.30 Hz; 3H).
E~ariiple 2 2-Ethoxy 3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6~7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoicacid / . I N~ / .. r, OH
N~~ ~ IOEt O
To a solution of ethyl 2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)'ethoxy)phenyl]propanoate (95 mg, 0.19'6 mmol) obtained in example 1 in methanol (10 niL) sodium carbonate (104 mg, . 0.98 minol) iiz water (10 mL) was added arid stirred at room 1s temperature for 12 h. Methanol vvas removed froru the reaction mixture under vacmun and the resulting aqueous layer was extracted with ethyl acetate. 'The aqueous layer vas acidified with 2N hydrochloric acid 'at low feiziperature.
The solids were filtered arid washe°d vaith cold water, dried under vacuum overnight to yield the title compound (60 W g~ 67 %); mp 171 °C.
1H NMR (CDC13) : 8 7.13 (d, J = 8.40 Hz, 2H), 6.77 (d, J = 8.60 I3z, 2I3), 4.50 (t, J= 5.00 Hz; 2H), 4.29 - 4.22 (m, SH), 4.01 (t, J = 3.70 Hz~ 1H), 3.69 -3.35 (m, 2H), 3.10-2.94 (m, 4H), 2.84 (t, J = 7.50 Hz, 2H), 1.90 - 1.78 (m, 2H), 1.38 (t, J = 7.30 Hz, 3H),.1.16 (t, J = 7.00 Hz, 3H), 0.97 (t, J = 7.40 Hz, 3H).
2s Example 3 Ethyl 3-[4-[2-(1,5-dimethyl=7-oxo-3-propyl=6;7-dihydro-III-pyrazolo [4,3-d]
pyrianidin-6-yl)ethoXy]phenyl]-2-ethoxypropanoate / ~ N~ ~ ~ OEt O ~, OEt ' s 'fhe title compound (200 mg, 58.4 %) was obtained as a white solid by condensing 1,5-dirfiethyl-3-propyl-6,7-dihydro-1H-pyrazolo[43~d]pyrimidin-7-one (150 mg, 0.728 mmol) obtained in preparation 8, with ethyl 3-[4-(2-bromoethoxy)phenyl]-2-ethoxyproparioate (502 riig., 1.45 mmol) prepared as disclosed in TJS patent application 091012,5'85 taken ' in dry N,N
1o dimethylformainide (3 mL,) in the presence of anhydrous K2~03 (300 mg, 2.18 mmol) for 24 h at room temperature following a sirriilar procedure as described in example 1, mp 120 °C.
IH NMR (CI7Cl3) : 8 7.10 (d, J = 8.40 Hz, 2H), 6.75 (d, J = 8.6b Hz, 2H), 4.47 (t, J= 5.00 Hz, 2H), 4.30 - 4.08 (m, 7H), 3.92 (t, J = 6.40 Hz, 1H), 3.65 -3.50 ~s (m, 1H), 3.39 - 3.25 (m, 1H), 2.91 (d, J = 6.30 Hz, 2H), 2.82 (t, J = 7.70 Hz;
2H), 2.75 (s, 3H), 1.90 - 1.70 (m, 2H), 1.20 (t, J = 7.30 Hz, 3I-3); 1.12 (t, J =
7.20 I-iz, 3H), 0.98 (t, J = 7.30 Hz, 3H1.
Exannple 4 20 3-[4-.[2~(1,5-Dimethyl-7-oXO-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid 0.
~. .I N ~ / i . 'OH
NCO. ~ OEt The title compound (74 mg, 78 %) Was obtained as a white solid from ethyl 3-[4-[2-( 1,5-dimethyl-7-oxo-3-propyl-6,7-dihydro-lI~-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]
phenyl]-2-ethoxyproparioate (134 mg, 0.258 mw o1) obtained in example 3 by s hydrolyzing in methanol-water (1 : 1, 20 W L) using sodium carbonate (112 mg, 1.06 minol) at room texiiperature for 24 h following a sunilar procedure as , described in example 2, mp 172 °C.
1H NMR (CDC13) : 8 7.13 (d, J = 8.30 Hz, 2H), 6.78 (d; J = 8.30. biz, 2H), 4.48 (t, J = 4:60 Hz, 2H), 4.35 - 4.15 (m, SH), 4.10 - 3.97 (ni; 1H); 3.56 -3.38 (m, 2H), 3.12 = 2.90 (in, 2H), 2.83 (t, J = 7.80 Hz; 21i), 2:76 (s, 3H); 1.89 -1.71 (m, 2~I), 1.16 (t, J = 7.00 Hz, 3H), 0.98 (t, J = 7.30 Hz, 3H).
Example 5.
Eth 1 2-ethox -3- 4- 2- 1-meth I-7-oXO-3 ro 1-5-tritluorometh 1-6 7 Y Y [ [ ( Y -P pY Y
~s dihydro-1H-pyrazolo[4,3-d]pyririiidin-6-yl)etho'xy]phenyl]propanoate OEt . N'N ~N~~ \ OEt The title compound (145 mg, 36 %) vas obtained by condensing 1-methyl-3-propyl-5-trifluoromethyl-6,7-dihydro-1~H-p'yrazola[4,3-d]pyrimidin-7-one (200 mg, 0.77 W mol) obtained in preparation 9, with ethyl 3-[4-(2-brow oethoXy)phenyl]-2-ethoxypropanoate (5'10 ing; 1.48 iizmol) prepared as disclosed in US patent application 09/012,585 taken in dry N,hT
dimethylformaniide (4 inl,) in the presence of anhydrous K2C03 (31 ~ mg, 2.30 mmol) for 48 h at room temperature following a sirizilar procedure as described iil example 1.
2s 1H NMR (CDC13) : 8 7.15 (d, J = 8.50 Hz, 2H), 6.84 (d, J = 8.50 Hz, 2H), 4:96 (t, J = 4.70 Hz, 2H), 4.38 (t, J = 4.50 Hz, 2H), 4.24-4.07 (m, SH), 3.95 (t, J

6.50 Hz, lII), 3.62-3.25 (m, 2H), 3.01 - 2.~6 (m, 4H), 1.89-1.72 (m, 2H), 1.21 (t, J = 7.00 Hz, 3H), 1.14 (t, J = 6.80 Hz, 3H), 0.98 (t, J = 7.30 I~z, 3H).
s Example 6 Ethyl 3-[4-[2-(5-bea~zyl=1-methyl=7-oxo=3-propyl-6,7-dihydro-11~-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2=ethoXypropanoate O
/ I N~Ph ~ i' ~, OEt .
N'N~N~.O ~ OEt 'The title compound (110 iilg, 56.8 %) was obtained as a liquid from 5=benzyl 1-methyl-3-propyl-6,7-dihydro-1H-pyrazolo[4,3=d]pyrimidin-7-one (100 mg, 0.354 mmol) obtained in preparation. 10, ethyl 3-[4-(2-broriZOethoxy)pheriyl]
2-ethoxypropanoate (159 mg, 0.46 mmol) prepared as disclosed in gJS patent application 09/012,585 and anhydrous K2C03 (146 rilg, 1.06 nimol) iri N,1V
dimethylformamide (2 mL) by following a sirriilar piocednre as described in Is example 1.
y (CHC13) : ~ 7.31-7.12 (m; 7H); 6.78 (d, J = 8.50 Hz, 2H), 4.46 (s~ .
2II), 4.33 (t, J = 4.80 Hz, 2H), 4.23-4.09 (m, 7H), 3.94 (tJ _ 6.60 Iiz, 1H), 3.63-3.28 (m, 2H), 2.99 - 2.80 (m, 4H), 1.90-L76 (m,,2H)1,.23 (t~ J = 7..10 Hz, 3H), 1.14 (t, J = 7.10 Hz, 3H), 1:01 (t, J = 7.30 Hz, 3H).
Example 7 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-lI3-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid ~ . I N~Ph j I OH .
N'N \N~~O \ , OEt 6s ~'he title compound (37 rng, 46 %) was obtained as solid frorii ethyl 3-[4-[2-(5-b enzyl-1-methyl-'7-oxo-3-propyl=6,7=dihydro=1 H-pyrazolo [4;3-d]pyrimidin-6-yl)ethoxy]phenyl]
-2-ethoxypropanoate (85 mg, 0.156 mmol) obtained in example 6 by hydrolyzing in riiethanol-water (1 : 1, 5 mL) using sodium carbonate (81 mg, 0.587 mmol) at room temperature for 17 h by following a similar procedure as described in example 2, Trip 149-151 °C.
1H NMR (CDC13) : S .7.32 - 7.13 (m, 7I~), 6.79 (d~ J = 6.50 Hz, 2H), 4.47 (s, 2H), 4.34 (t, J = 4.90 Hz, 2H), 4.24-4.19 (m, SH), 4.05 (dd; J = 4.40 and 7.10 Hz, 1H), 3:63-3.37 (m, 2H), 3.13 = 2.85 (in, 4H); 1:89-1.72 (iii9 2H); 1.18 (t, J
= 7.00 Hz, 3H), 1.02 (t, J = 7.30 Hz, 3H).
Example 8 Ethyl 3- [4= [2-(5-b enzyl-1-methyl-7-oXO-3-propyl-6,7-dihydro-1H-is pyr~zolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ph'enox~propanoate / I N~Ph ~ ~ pEt N'N NCO \ OPh . ~ O
The title compound (180 mg, 85.4 %) was obtained as a liquid from 5-benzyl- , 1-methyl-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-'7-one (100' iiig, 0.35 mmol) obtained in preparation 10, ethyl 3-[4-(2-br'orrioethoxy)phenylj-2-20 ~ phenoxypropanoate (278 mg, 0.70 mmol) and anhydrous KZC03 (145 ing, 1.05 mmol) as a base by following a similar proceduredescribed in example 1.
1H NMR (CI~Cl3) : b 7.30-7.15 (ril, 9H), 6.93 - 6.75 (m, SH); 4.72 (t; J =
6.50 Hz, 1H), 4.46 (s, 2H), 4.33 - 4.10 (m, 9H), 3.17 (d, J = 6.60 Hz~, 2H), 2.88 (t, J
= 7.50 Hz, 2H), 1.90-1.75 (m, 2H), 1.19 (t, J = 7.10 Hz, 3H), 1.01 (t, J =
7.30 2s Hz, 3H).

Example 9 Ethyl 3-[4-[2-(5=ethyl-1-methyl=7-oxo-3-propyl-6,7=dihydro-1~I=pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoXypropanoate N~ ( (V~ /, I OEt .
,~ NCO, ~ OPii , ~ ~
s The title compound (450 mg, 74.5 %) was obtained as a solid from 5-ethyl-1-methyl-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-7-one (250 mg, 1.136 mmol) obtained in preparation 7, ethyl 3-[4-(2-broxrioethoXy)phenyl]-2-phenoXypropanoate (670 mg, 1.70 m~nol) arid anhydrous K2C03 (470 mg, 3.40 uilmol) as a base by following a similar procedure as described ,in 1o example l, mp 84-86 °C.
1H NMR (CD'Cl3) : 8 7.22-7.17 (m, 4H), 6.97 - 6.76 (m, SH), 4.71 (t, J = 6.50 Hz, 1H), 4.49 (t, J = 5.10 Hz, 2H), 4.28-4.10 (m, 7H), 3.16 (d, J = 6.60 Hz, 2H), 3.04 (q, J = 7.30 liz, 2Ii), x,.85 (t, J = 7.60 Hz, 2H), 1.90 _ 1.73 (iii, 2H), 1.38 (t, J = 7.30 Hz, 3H), 1.18 (t, J = 7.10 Hz, 3H), 0.99 (t; J = 7.30 ~Iz, 3H).
is example 10 3-[4-[2-(5=Ethyl-1-amethyl-7-oxo-3=propyl-6,7-dihydro-1gI-pyrazolo[4;3-d] .
pyrimidin-6-yl)ethoXy]phenyl]-2-phenoxypropanoic acid O
/ i N\ ~ / I. ~H
N~N ~N'~' O ~ OPh 20 The title compound (246 mg, 78 %) 'was obtained as a solid from ethyl 3-[4-[2-(S-ethyl=1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidiri=6-yl)'ethoxy]phenyl]

-2-phenoXypropanoate (330 rrig, 0.620 mmol) obtained in example 9 and sodium carbonate (328 mg, 3.10 rnmol) as a base in methanol-water (1 : 1) by following a similar procedure as described in example 2, mp 148-150 °C.
lI~ NMR (CDCl3) : ~ 7.21 (broad s, 4H), 6.98 - 6.70 (m, SH), 4.77 (broad s, s 1H), '4:47 - 4.20 (m, 7H), 3.20 - 2.79 (m, 6I~), 1.84-1.73 (rig, -2H), 1.36 (t, J
7.0~ Hz, 3H), 0.97 (t; J = 7.20 Hz, 3H). .
Example 11 Ethyl 3-[4-[2-(1,5-dimethyl-7-oxo-3-propyl-6,7-dihydro=1H-pyrazolo [4,3-io d]
pyrimidiri-6-yl)ethoxy)phenyl]-2-phenoxyprop'ahoate ~ ' o N/' I N_ / / I, OEt .
'N ~N~O \ OPh The title compound (250 mg, 69.4 %) was obtained as a v~%hite 'solid from I,S-dimethyl-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidiri-7=one (150 mg, , is 0.694 mmol) obtained in preparation 8, ethyl 3-[4-(2-biomoethoxy)phenyl]-2-phenoxypropanoate (546 ing, 1.39 mmol) and anhydrous KZC03 (192 mg, 1.39 minol) as a base by following a similar procedure as described in example l, mp 128 - 132 °C. , 1H N1VIR (CDCl3) : 8 7.20 (d, J = 7.30 $-Iz, 4I-i), 6.95 = 6.75 (in, SH), 4.71 (t, .
2o J= 6.50 Hz, 1H), 4.48 (t, J = 4.70 Hz, 2H), 4.29 - 4.11 (rim; 7H); 3.16 (d, J
6.60 Hz, 2H), 2.84 (t, J = 7.20 Hz, 2H), 2.76 (s, 3H), 1.90 - 1.71 (m~ 2H), 1.19 (t, J = '7.10 Hz, 3H), 0.99 (t, J = 7.30 Hz, 3H).
Example 12 2s 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-lH-py~azolo[4,3-d]
pyriW idin-6-yl)ethoxy]phenyl]-2-phenoxyproparioic acid O
N~ I N~ /-I OH
'N N~ ~~ ~ . OPh , O
The title compound (100 mg, 75.5 %) was obtained as a white solid froril ethyl 3-[4-[2-( 1,5-dirriethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4~3-d]pyrimidin-6-yl)ethoxy]
phenyl]-2-phenoxypropanoate (150 mg, 0.270 mmol) obtained in example 11 and sodiuri~ carbonate (143 ring, 1.35 mmol) as a base in rriethanoY-water (5 : 1, 12 inL) by following a siriiilar procedure as described in example 2, mp 172-174 °C.
1H NMR (CDCl3) : 8 7.20 - 7.15 (rim, 4H), 6.96 - 6.72 (n1; SH), 4.75 (t; J =
5:80 Hz, 1H), 4.50 - 4.40 (m, 2H), 4.24 (t, J = 5:00 Hz, 2H), 4:18 (s, 3H);
3.17 (d, J = 5.60 Hz, 2H), 2.80 (t, J = 7.50 Hz, 2H), 2.72 (s, 3H), 1.83 =
1.67 (m, 2H), 0.96 (t, J = 7.30 Hz, 3H).
example 13 ethyl 3-[4-[2-(3,5-dipropyl-1-methyl-7-oxo=6,7-dihydro-1~I-pyrazolo[4,3-d]
pyrimid'in-6-yl)ethoxy]phenyl]-2-ethoXypropanoate N / I N ~ / I O,Et 'N NCO \ OEt The title compound (240 mg, 57.1 %) vvas obtained as a white solid by lxeating , 3,5-dipropyl-1-rizethyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrirriidin-7=one (200 mg, . 0.855 mmol) obtained inpreparation 11, with ethyl 3-[4-(2 bromoethoxy)phenyl]-2-ethoxypropanoate (737mg, 2.1'4 mW o1) prepared as disclosed i11 US patent application 09/012,585 taken in dry N,N
dimethylformamide (4 inL) in the presence of anhydrous K2C03 (360 mg, 2.56 mmol) as a base for 48 h at room temperature by following a siuiilar procedure as described in example 1, mp 110 - 114 °C.
1H (CDCl3) : ~ 7.12 (d, J = 8.50 biz, 2H), 6.75 (d, J _ x.50 Hz, 2H), 4.48 (t, J= 5.10 Hz, 2H), 4.28 - 4.13 (m, 4H), 4.21 (sa 3H), 3.92 (t, J = 6.40 Hz;
s 1H), 3.65 - 3.22 (m, 2H), 3.00 - 2.79 (m, 6H), 1.95 -1:70 (m, 2H), 1.21 (t, J =
7.20 ~Hz, 3H), 1.13 (t, J = 6.90 Hz, 3II), 1.06 (t, J = 7.20 Hz; 3H), 0.98 (t, J =
7.30 Hz, 3H).
Example 14 to 3-[4-[2-(3,5-Dipropyl-1-methyl-7-oxo=6,7-dihyd~o-1~1f-py~azolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2=ethoxypropanoic acid ~ IN~ ~ i ova , , N°N ~ N ~~ \ OEt O
'The title compound (75 mg, 66.2 %) wa's obtained as a white solid from ethyl 3-[4-[2-(3, ~=dipropyl-1-methyl-7-oxo-6, 7-dihydro- l I~=pyrazolo [4,3-1s d]pyrimidin-6-yl)ethoxy]
phenyl]-2-ethoxypropanoate (120 ring, 0.241 mriiol) obtained m example 13 and sodium carbonate (128 ing, 1.20 mmol) as a base in methanol-water (5 : 1, 12 mI,) reacting foi' 48 h at room temperature by following a sirriilar procedure as described in example 2, mp 160-161 °G.
20 1H IVMR (GDC13) : 8 7.13 (d, J = 8.30 Hz, 2H), 6.78 (d, J = 8.x'0 Hz, 2H), 4.49 (t, J= 5.10 Hz, 2H), 4.29 - 4.22 (m~ SH), 4.10 - 3.98 (m, 1H), 3.65 - 3.40 (m, 2H), 3.12 - 2.80 (m, 4I~f), 1.95 - 1.75 (m, 4H), 1.17 (t, J _ ~ 7.00 Hz, 3H), 1.07 (t, J = 7.50 Hz, 3H), 0.99 (t, J = 7.50 Hz, 3H).
2s Exmnple 15 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-.
pyrimidih-6-yl)ethoxy]phenyl]-2-pliemoXypropanoic acid O
/ N~Ph ~ 1 OH
N'N~N~O W I OPh I
O
s The title compound (65 mg, 52.3 %)~was obtained as a solid frorii ethyl 3-[4-[2-(5-benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4~3-d]pyriiiiidin-6-yl)ethoxy]
phenyl]-2-phenoxypropanoate (130 mg; 0.219 mmol) obtained in exaW ple 8 and sodium carbonate (116 mg, 1.09 mriaol) iri methanol-water (1 a 1) by following a similar procedure as described in example 2, m~ 6$-72 °C.
1H NMR (CDCl3) : 8 7.29-7.18 (m, 9H), 7.03-6.76 (m, SH), 4:82 (t, J= ~6.5b Hz, 1H), 4.45 (s, 2H), 4.36 - 4.10 (m, 7H), 3.22 (d, J = 5.90 ~Iz, 2H), 2.88 (t, J
= 7.80 Hz, 2H), 1.90 -1.75 (m, 2H), 1.00 (t, J -- 7.30 Hz, 3H).
is example 16 Ethyl 3-[4-[2-(3,5-dipropyl-1-methyl-7-oxo-6,7-dihydro-ll~I-pyfazolo [4,3-d]
pyrimidiri-6-yl)ethoxy]phenyl]-2-phenoxyproparloate ~ ~ N~ / I OEt N'N N~ ~'' O ' ~ OFh .
~ O
20 The title coW poW d (29'6 mg, 63.5 %) was obtained as a yvhite solid from 1-methyl-3,5-dipropyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-7-one (200 rng, , 0.855 mmol) obtained in preparation 11, ethyl 3-[4-(2-bromoethoxy)phenyl]-2-phenoxypropanoate (1.16 g, 2.95 mmol) and K~C03 (0.59 g, 4.27 mmol) in dry N,N dirriethylformamide (7' mL) by followiilg a similar procedure described in example 1, mp 82 °C.
1H NMR (CDCl3) : b 7.21-7.17 (m, 4H), 6.92 - 6.75 (m, SH), 4.70 (t, J =
5.60 Hz, 1H), 4.48 (t, J = 5.00 Hz, 2H), 4.28 - 4.11 (m, 7H), 3.15 (d, J =
6.30 s Hz, 2H), 2.97 (t, J = 7.70 Hz, ZH), 2.84 (t, J = 7.30 Hz, 2H), 1.95-1.75 (m, 4H), 1.18 (t; J = 7.10 I-Iz; 31-I), 1.06 (t, J = 7.30 IIz; 3H), 0.98 (t,~ J =
7.f0 Hz;
3H) Example 17 ;
io 3-[4-~2-(3,5-Dipropyl-1-methyl-7-o~0-6,7-dilaydro-lI~-py~az~'lo[4,3=
d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxyproparioic acid O
N~ I N~ /.,,I OH , 'N N~ ~'' O \ OPh ~ O
The title compound (207 mg, 88 %) was obtained as a White 'solid from ethyl 3-[4-[2=(3;5-dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolb[4;3-is d]pyrimidin-6-yl)ethoxy]
phenyl]-2-ethoxypropanoate (246 mg, 0.450 mmol) obtaiiized in eXample 16 and sodium caiboriate (239 mg, 2.25 mmol) in rriethanol-water (10 : l, 33 rriL) by following a similar procedure as described in e~aniple 2, riip 159-163 °C.
1H NMR (CDC13) : b 7.24-7.16 (m, 4H); 6.92 - 6.73 (m; SH), 4.74 (t; J= 5.60 2o Hz, 1H), 4.46 (t, J _ 4.60 Fiz, 2H), 4.27 - 4.1r8 (m, 2H)~ 4.19 (s; 3H);
3.16 (d, J = 5.10 Hz, 2H), 2.95 (t.; J = 7.30 Hz,. 2H), 2.82 (t, J = 7.50 Hz; 2H), 1.95 1.72 (m, 4H), 1.04 (t, J = 7.30 Hz, 3H), 0.97 (t; J = 7.50 Hz; 3I-I).
Example 18 72 ' , [2R, N(1S)]-2-ethoXy-3-[4-[2-(5-ethyl-1-iriethyl-7-oxo-3-propyl-6,7-dihydro=1~I-py~azolo [4,3-d] pyrirriidin-6-y] ethoXy] phenyl] -N-(2-hydroxy-1-phenylethyl) propanamide (18 A) Ph , ~ N~ /' _ N~'pH
i N ~O \
N ~ I H. H
O .
[2S9 N(1S)]-2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1FI-pyrazolo [4,3-d] pyrimidin-6-y] etho~y] phenyl]-N-(2-hydroxy-1-Phenylethyl) propanamide (f8 B) O Ph / N~ ~ ~ N~OH
,N NCO \ O~.
N ~ I H' ~ ~ H
O
To a cold solution of S(+)=2-phenylglycinol (390 mg., 2.85 mmol) in dry dichlorometh'ane (10 mL), triethyl amine (0.79 mL, 5.7~ riimol) was added dropwise and stirred for 15 min at 0 °C. In ~. sep'arate arrangement to a solution of 3-[4-[2-(5-ethyl-1,-methyl-7-oxo-3-propyl-67-dihydro-1H
1s pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]
phenyl]-2-ethoxypropanoic acid (1.3 g, 2.85 mmol) ob'taiiied in example 2 in dry dichloromethane (10 mL) at 0 °C triethyl amine (0.99 ailI,, 7.12 W
mol) was added and stirred for 15 min. To this solution pivaloyl chloride (0.386 mL, 3.136 mmol) was added dropwise and stirred for 3'0 min at °C. This mixture was added to the phenylglycinol rriixture dropwise at 0 °C arid stirred for 1 h at that temperature. The reaction mixture was stirred overnight at room temperature. The organic phase was washed with water, dried (Na2S04) and evaporated to dryness. The residue vas purified by silica gel column chromatography using 60 % ethyl acetate in pet ether - 100 % ethyl acetate as an eluent to afford a diasterebmer tentatively assigned as [2R; N( 1 S)]-2-ethoxy-3-[4-[2-(S-ethyl-1-methyl-7-ono-3-propyl-6,7-dihydro-1H- °
pyrazolo[4,3-d]pyrimidin-6-y]ethoxy]phenyl]-N-(2-hydroxy-1-' phenylethyl)propanamide (18 A) (500 mg, 30.5 %), mp 138-139 °~C
followed s by [2S, N(1S)]-2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo=3-propyl-6,7 dihydro-1H-pyrazolo[4;3-d]pyrimidin-6-y]ethoxy]phenyl]-N=(2-hydroxy-1- .
phenylethyl) propanamide (18 B) (400 mg, 24.4 %), mp 182-183 °C.
18A : [a]z5D - +20.2° (C = 0.5, GHC13); 1H NMR (CDC13) ~ : 7.32 - 7.27 (m, no 4H), 7.16 (d, J = 8.5'0 Hz, 2H), 7.00 (d, J = 7.30 Hz, 1H), 6~80(d~ J =
8.30 ~Iz, 2H), 5.05 - 4.89 (m, 1H), 4.51 (t, J = 5.00 I-Iz, 2I~); 4.2~ (t, J _ 4.80 Hz9 2H), ;
4.22 (s, 3H), 3.95 (dd, J = 3.90 and 2.20 I~z, 1H), 3.67 - 3.62 (m, 2H), 3.48 (q, J = ~ 7.20 Hz, 2H), 3.12 - 2.92 (m, 4H), 2.86 (t, J = 7.50 Hz, 2H), 1.91 -1.75 (m, 2H), 1.39 (t, J = 7.30 Hz, 3H), 1.13 (t, J = 6:90 Hz, 3H), 1.00 (t, J =
7.30 is Hz, 3JE1)..
18~ a [~]z5D - _ 12.6° (C= 0.5, ~ CHC13); 1~I NMR (CDCl3) 8 : 7.23 -7.01 (m, 7H), 6.68 (d, J = 8.50 Hz, 2H), 5.06 - 4.90 (m, 1H), 4.51 (t, J = 5:00 Hz, 2H), 4.27 - 4.22 (m, SH), 3.96 (dd, J = 4.00 and 2.90 Hz, 1H), 3.84 (d, J = 4.20 Hz, 2H), 3.60 - 3.45 (m, 2H), 3.13 = 2.75 (m, 6H), 1.91-1.78 (iri, 2H), 1.39 (t, 2o J = 7.30 Hz, 3H), 1.13 (t, J = 7.00 Hz, 3H), 1.00 (t, J = 7:3~ Hz, 3H).
Example 19 (+) 2-Ethoxy 3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1FI-pyrazolo 2s [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoic acid ~, IN~ ,,I
N I;
,I~N~O \ H O
p [2R, N(1S)]-2-ethoxy-3-[4=[2-(5-ethyl-1-methyl-7-oXO-3-p~ropyl-6,7-dihydro-1 H-pyrazolo [4, 3-d]pyririlidin-6-y] ethoxy]phenyl]-N-(2-hydroxy- I
phenylethyl)propanarilide (300 mg, 0.52 mmol) obtained in example 18A was taken in a mixture of dioxane (1.4 mL), water (1.4 W L) and 1M sulfuric acid s (1.36 mL) at room temperature and stirred under reflux for 34 h. Water and dioXane were removed under vacuum. The residue was ~ t'aken iri water arid extracted with ethyl acetate and the 'ethyl acetate layer was washed with water, dried (NaaS04) and evaporated to diyness to yield the ciltde compound. The crude compound Was purified by column chroriiatography using 50 % ethyl acetate in p'et. ether as an eluent to afford the title compound. (120 mg, 50.6 %) mp 144=145 °C.
[a,]ZSD = 17.2° (c = 0.5, CH3~H); 1H NMR (CL~Cl3) : b 7.12 (d, J = 8.50 Hz, 2H), 6.76 (d, J = 8.50 Iiz, 2H), 4.49 (t, J = 5.00 I~z, 2H), 4:28 - 4.21 (m, 5H), 4.01 (dd, J = 4.50 and 2.90 Hz; 1H), 3.65-3.33 (m, 2H), 3.12 - 2.90 (m, 4H), ~5 2.84 (t, J = 7.50 Hz, 2H), 1.90 -1.74 (m; 2~I), 1.37 (t, J = 7.30 Hz, 3H), 1.15 (t, J = 7.10 Hz, 3H), 0.98 (t, J = 7.30 Hz; 3H).
Example 20 (=) 2-Ethoxy 3-[4-[2-(5-ethyl-1-methyl-'7-oxo-3-propyl-6,7-dihydxo-lI3-2o pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoac acid O
OH
NCO w p O
The title 'compound (69 mg, 48.3 %) was obtained by hydrolyzing [2S, N(1 S)]-2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-25 pyrazolo[4,3-d]pyrimidin-6-y]ethoxy]phenyl]-N-(2-liydroxy-1- .
phenylethyl)propanainide (180 mg,. 0.31 mmol) obtained im example 18 B

using dioxane ( 1.1 mL), water ( 1.10 mL) and 1M sulfuric acid ( 1.00 mL,) following a similar procedure describe"d in example 19, iiip 134-136 °C.
[a,]2$D = -17.6° (c = 0.5, CH30H); 1H NMR (CDCl3) : ~ '7.13 (d~ J =
8.50 Hz, 2H), 6.77 (d, J = 8.50 Hz, 2H), 4.50 (t, J = 5.10 I~z, 2H), 4.29 - 4.22 (m, SH), s 4.02 (dd, J = 4.40 and 2.90 Hz, 1H), 3.63-3.38 (m, 2H), 3.10 - 2.94 (m, 4H), 2.85 (t, J = 7.40 Hz, 2H), 1.86 -1.75 (rim, 2H), 1.38 (t, J = 7.30 Hz, 3H), 1.16 (t, J = 7.10 Hz, 3H), 0.99 (t, J = 7.30 Hz, 3H).
The compounds of the present invention lowered random blood sugar level, triglyceride, total cholesterol, LDL, VLDL and increased HDI,. This was demonstrated by ih vitro as well as ih vivo animal expeririients. ..
Demonstration of Efficacy of Compounds a is f1) Iya vitro a) Determination of hPPAl2oc activity,:
Ligand binding domain of hPPARa was fused to I7NA binding domain of Yeast transcription factor GAL4 in eucaiyotic expression ~ vector. ~Jsing superfect (Qiagen, Germany) as transfecting reagent HEK-293 cells W ere 20 transfected v~ith this plasmid and. a reporter plasmid harboring the lizciferase gene driven by a GAL4 specific promoter. Compour_d was added at different concentrations after 42 hrs of transfection and incubated overnight.
Luciferase activity as a function of compound binding/activation capacity of PPAIW was measured using Packard Luclite kit (Packard, USA) in Top Count (Ivan 2s Sadowslci, Brendan Bell, Peter Broag and lVlelvyn Hollis. Gene. 1992. 118 :
137 -141; Superfect Transfection Reagent Handbook. Febiuary 1997. Qiagen, Germany).
b) Determination of hPPAR~y activity a Ligand binding domain of hPPARyl was fused to I~NA Binding domain of Yeast transcription factor GAL4 in eixcaryotic expression vector. Using lipofectamine (Gibco BRL, USA) as transfecting reagent HEK-293 cells were transfected with this plasmid and a reporter plasmid harboring the luciferase s gene driven by a GAL4 specific promoter. Compound was added at 1 p,M
concentration after 48 hrs of transfection and incubated overnight. Luciferase activity as a function of drug binding/activation capacity of PPARyl vvas measured using Packard Luclite kit (Packard, USA) in Packard Top Count (Ivan Sadowski, Brendan Bell, Peter Broag and Melvyn Hollis. (Gene. 1992.
118 : 137 -141; Guide to Eukaryotic Transfections with Cationic Lipid Reagents. Life Technologies, GIBC~ BRL, USA).
PPARa and $PARy,activity ' Example No ConcentrationPPARoc ConcentrationPPARy Example 1 50 ~M 5.00 1 p,M 11.0 Example 3 50 pM 6.9 1 ~M 19.0 Example 4 50 p..iM 8.32 l ~,M 14.6 c) Deteranination of HldIG CoA reduetase inhibition activity o Liver 15 microsorile bound reductase was prepared from 2% cholestyramine fed rats, at raid-dark cycle. Spectrophotometric assays were carried out iri 100 mM
KH2PO4, 4 mM 17TT, 0.2 mM NADPH, 0.3 ri~lVl HMfG CoA and 125 ~,g of liver . microsoiilal enzyme. Total reaction mixture volume was kept as 1 ml.
Reaction was started by addition of HMG CoA. IReaction mixture was 2o incubated at 37 °C for 30 min and decrease in abs'orbarice at 340 nm was recorded. Reaction mixture without substrate was used as blamk (Goldstein, J.
L and Brown, M. S. Progress in understanding the LDL receptor and HMG
CoA reductase, two membrane proteins that regulate the plasma cholesterol. J.

Lipid IRes. 1984, 25: 1450 - 1461). The test compounds inhibited the HMG
CoA i'eductase enzyme.
dfZ vavo : ' s a), Efficacy in genetic models Mutation in colonies of laboratory animals' and different sensitivities to dietary regimens have made the development 'of animal models with non-insulin dependent diabetes and hyperlipidemia associated with obesity and insulin resistance possible. Genetic models such as db/db and ob/ob (Diabetes, (1982) 31(1) : 1- 6) mice and zuckei- fa/fa rats Have been developed by the various laboratories for understanding the pathophysiology of disease and testing the efficacy of netu antidiabetic cora~pounds (Diabetes, (1983) 32:
830-838 ; Annu. Rep. Sankyo Res. Lab. (1994). 46 : 1-57). The homozygous animals, C57 BL/KsJ-db/db mice developed by Jackson Laboratory, US; are 1s obese, hyperglycemic, hyperinsulinemic and insulin resistant (J. Olin.
Invest., ' (1990) 85 : 962-967), whereas heterozygous are lean and normoglycemic. In db/db model, mouse progressively develops insulinopenia vs%ith age, a feature commonly observed in late stages of human type II diabetes when blood sugar levels are insufficiently controlled. The state of pancreas and its course vary 2o according to the models. Since this model resembles that of type II
diabetes mellitus, the compounds of the present invention were tested for blood sugar and triglycerides lowering activities. , _ ,. .
Male C57BL/KsJ-db/db mice of 8 to 14 weeks age; Having body weight range of 35 to 60 grams, bred at Dry Reddy's Research Foundation (I~RF) 2s animal house, were used in the experiment. The rriice were provided with standard feed (National Institute of Nutrition. (NIN), Iiyderabad, India) and acidified water, ad libitum. The anirrials having more than 350 mg / dl blood sugar were used for testing. 'The number of aniW als in each group was 4.

Test compounds were suspended on 0.25 % carboxymethyl cellulose and administered to test group at a dose of 0.001 mg to 30 'xng / kg through oral gavage daily for 6 days. The control group received vehicle (dose 10 inl /
kg). On 6th day the blood samples were ~ collected one hour after s administration of test compounds '/ vehicle for assessing the biological activity.
The random blood sugar and triglyceride levels were measured by collecting blood (100 ~l) through orbital sinus, using heparinised capillary in tubes containing EDTA which was centrifuged tm obtain plasrria: The plasma glucose and triglyceride levels' were riieasured spectrometrically, by glucose oxidase and glycerol-3-P04 oxidase/peroxidase enzyme (Dr: Reddy"s Lab.
Diagnostic Division Kits, Hyderabad, India) methods respectively.
The blood sugar and triglycerides lowering activities of the test compound was calculated according to the forrriula.
~s No adverse effects were observed for any of the rrientioned compounds of invention in the above test.
BLOOD GLUCOSE LOWERING ACTIVITY IN DB/DB MICE
Compound Dose (mg / Reduction in Triglyceride . kg) Blood Lovc~ering Glucose Level (%) (%) Example 3 mg 58 23 Exarizple 3 mg 42 . 17 Example 3 mg 33 35 2o The ob/ob mice were obtained at 5 weeks of age from Bomholtgard, Denmark and were used at 8 weeks of age. Zucker fa/fa fatty rats were obtained from IffaCredo, France at 10 weeks of age arid were used at 13 weeks of age. The animals were maintained under 12 hour light and dark cycle at 25 + 1 °C. Animals we're given standard laboratory chow (NIN, Hyderabad, 2s India) and water, ad libitum (Fujiwara, T., Yoshioka; 5., Yoshioka, T., LTshiyama, I and Horikoshi, H. Characterization of new oral antidiabetic agent CS-045. Studies in KID and ob/ob mice and Zucker fatty rats. Diabetes. 1988.
37 : 1549 -1558).
s The test compounds were administered at 0.1 to 30 mg/kg/day dose for 9 days. The control animals received the vehicle (0.25 carboxymethylcellulose; dose 10 ml/kg) though oral gavage.
The blood samples were collected in fed state 1 hour after drug administration on 0 and 9 day of treatment. The blood was collected from the 1o retro-orbital sinus through hepaririised capillary iii EFTA containing tubes.
After centrifugation, 'plasma sample was separated for triglyceride, glucose, free fatty acid, total cholesterol arid insulin estimations: Measurement of plasma triglyceride, glucose, total cholesterol were done using commercial kits (17r. Reddy's Laboratory, Diagnostic I3ivision kits, fIyderabad, India).
is The plasma free fatty acid was measured using a commercial kit form Boehringer Mannheim, Germany. The plasma insulin ~uas measured using a RIA kit (BARC, India). The reduction of various parameters examilied are calculated according to the formula.
In ob/ob mice oral glucose tolerance test was performed after 9 days 2o treatment. Mice were fasted for 5 hrs and challenged with 3 gin%kg of glucose orally. The blood samples were collected at 0', 15, 30, 60 arid 120 min for estimation of plasma glucose levels.
The experiiiaental results from the db/db mice, ob/ob mice, Zucker fa/fa rats suggest that the novel compounds of the present invention also possess 25 therapeutic utility as a prophylactic or regular treatment for diabetes, obesity, cardiovascular disorders such as hypertension, hyperlipidaeniia and other diseases; as it is known from the literature that such diseases are interrelated to each other.

Blood glucose level and triglycerides are also lowered at doses greater than 10 rizg/kg. Normally, the quantum of 'reduction is dose dependent and plateaus -at certain dose.
s h) Cholesterol lowering activity in hypercholesterolemic.rat models a Male Sprague Dawley rats (NII\T stock) were bred in DRF animal house. Animals were maintained under 12 hour light and dark 'cycle at 25 ~ 1 °C. Rats of 180 - 200 gram body weight range were used for the experiment.
Animals were made hypercholesterolemic by feeding 2% cholesterol and 1%
no sozlium cholate mixed with standard laboratory chow [National Institute of Nutrition (NINA, Iiyderabad, India] for 6 days. Throughout the experimental period the animals were maintained on the same diet (Pent; D., Bonnefis, M.
T,, Rey, C and Infante, R. Effects 'of ciprofibrate on liver lipids and lipoprotein synthesis in normo- and hyperlipidemic rats. Atherosclerosis. 198. 74 : 21~
ls 225).
The test compounds were administered orally a't a dose 0.1 t~ 30 mg/kg/day for 3 days. Control group was treated With vehicle alone (0.25 Carboxyrnethylcellulose; dose 10 ml/kg).
The blood samples were collected in fed state 1 hour after drug 2o administration on 0 and 3 day of compound treatment: The blood was collected from the retro-orbital sinus through heparinised capillary in EDTA
containing tubes. After centrifugatidr~, plasma sample was separated for total cholesterol, HDL and triglyceride estimations. Measurement of plasma triglyceride; total cholesterol and HDL were done using commercial kits (Dr.
2s Reddy's Laboratory, Diagnostic Division, India): LDL and VLDL cholesterol were calculated from the data obtained for total cholesterol, HDL and triglyceride. The reduction of various parameters examined are calculated according to the formula.

CHOLESTEROL LOWERING ACTIVd'I'Y IN MALE SPRAGgJE
DAWLE~' RAT MODELS
Compound Dose TriglycerideTotal HDL LDL VLDL

mg/kg (%)~ CholesterolT (%

(%)~, (%) Example 3 mg 70 60 164 72 71 s c) Plasma tri~lyceride and total cholesterol Idwerin~ activity in Swiss albino micea Male Swiss albino mice (SAlV~ and male Guinea pigs were obtaimed from NITT and housed in DRF animal house. All these animals were to maintained under 12 hour light and dark cycle at 25 ~ 1 °C. Anuiials were given standard laboratory chow (NIN, Hyderabad, India) and water, _ ad libitum. SAM of 20 - 25 g body weight range and Guinea pig's of 500 - 700 g body weight range were used (Olives, P., Plancke, M. O:, IVIarzin, D., Clayey, V., Sauzieres, J and Fruchart, J. C. Effects of fenofibiate, geriifbrozil and is nicotinic acid on plasma lipoprotein levels in normal and hyperlipidemis micea Atherosclerosis. 1988. 70 : 107 -114).
The test compounds were administered orally to Swiss albino mice at 0.3 to 30 mg/kg/day dose for 6 days. Control mice were treated with vehicle (0.25% Carboxymethylcellulose; dose 10 ml/kg). The test compounds were 2o administered .orally to Guinea pigs at 0.3 to 30 mg/kg/day dose for 6 days.
Control animals were treated with vehicle (0.25% Carboxyiiiethylcellulose;
dose 5 ml/kg). ' The blood samples were collected in fed state 1 ho r after drug administration on 0 and 6 day of treatment. The blood was collected from the 2s retro-orbital sinus through heparinised capillary in EDTA containing tubes.
After centrifugation, plasma sample .was separated for triglyceride and total cholesterol (~7Vieland, O. Methods of Enzymatic analysis. Bergermeyer, FI. O., Ed., 1963. 211 - 214; Trinder, P. Ann. Olin. Biochem: 1969. 6 : 24 - 27).
Measurement of plasrria triglyceride, total cholesterol and HDL were done using commercial kits (Dr. Reddy's Diagnostic Division, Hyderabad, India).
s TRIGLYCE1RIDE LOWERING ACTIVITY IlV SWISS ALBINO
MICE
Corripound Dose (mg / Triglyceride kg) Example 3 mg 45 Example 3 mg 61 Example 3 mg 66 Example 3 mg 25 Formulae for calculatiota 1. Percent reduction in Blood sugar / triglycerides l total cholesterol were calculated according to the formula Percent reduction (%) = 1 _ TT / OT ~ 100 T~/OC
OC =Zero day control group value is OT = Zero day treated group value TC = Test'day control group value TT = Test day treated group value 2. LDL arid VLDL cholesterol levels were calculated according to the 2o formula Triglyceride LIJL cholesterol in mg/dl = [ Total cholesterol - HIOL cholesterol '- ] mg/dl VLDL cholesterol in mgJdl = [Total cholesterol - HDL cholesterol - LPL
cholesterol] mgldl.

Claims (64)

Claims

1. A compound of formula (I) its derivatives, its analogs, its tautomeric forms, its stereoisomers, its polymorphs, its pharmaceutically acceptable salts, its pharmaceutically acceptable solvates, where R1 represents hydrogen atom, halogen, hydroxy, lower alkyl, alkoxy, substituted or unsubstituted aralkyl group or forms a bond together with the adjacent group R2; R2 represents Hydrogen, hydroxy, halogen, lower alkyl, alkoxy, alkanoyl; aroyl, aralkanoyl, substituted or unsubstituted aralkyl or R2 forms a bond together with R1; R3 may be Hydrogen atom or substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, alkanoyl, amyl, aralkyl, heterocyclyl, heteroaryl, heteroaralkyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl groups, with a provision that R3 does not represent hydrogen when R4 represents hydrogen or louver alkyl group; R4 may be hydrogen or substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroalkyl or heteroaralkyl groups;
Y
represents oxygen or NR5, where R5 represents hydrogen or substituted or unsubstituted groups selected from alkyl, aryl, aralkyl, hydroxyalkyl, alkanoyl, aroyl, aralkanoyl, heterocyclyl, heteroaryl or heteroalkyl groups; R4 and R5 together may form a substituted or unsubstituted 5 or 6 membered cyclic structure containing carbon atoms, a nitrogen atom and which may optionally contain one or more additional heteroatom's selected from oxygen, sulfur or nitrogen; n is an integer ranging from 1- 4; Ar represents substituted or unsubstituted, divalent, single or fused, aromatic or heterocyclic group; A
represents a cyclic structure given below:

where X represents O or S; R6 when attached to the carbon atom represents hydrogen, halogen, hydroxy, nitro, cyano, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl;
amino, acylamino, monoalkylamino, dialkylamino, arylamino; aralkylamino;
aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R6 when attached to nitrogen atom represents hydrogen, hydroxy, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy; aryl, aralkyl, aryloxy, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, amyl,alkanoyloxy, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl groups, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R7 and R8 when attached to carbon atom may be same or different and represent hydrogen, halogen, hydroxy, cyano, nitro, formyl or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxyalkyl, thioalkyl, alkylthio groups;
R7 and R8 when attached to nitrogen may be same or different and represent hydrogen, hydroxy or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino groups.

2. A compound of formula (I) according to claim 1, wherein the groups represented by R3 are substituted, the substituents may be selected from halogen, hydroxy or nitro or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aralkyl, aralkoxyalkyl, heterocyclyl, heteroaryl, heteroaralkyl, alkanoyl, alkanoyloxy, hydroxyalkyl, amino, acylamino, arylamino, aminoalkyl, aryloxy, alkoxycarbonyl, alkylamino, alkoxyalkyl, alkylthio, thioalkyl groups, carboxylic acid or its derivatives, or sulfonic acid or its derivatives.

3. A compound of formula (I) according to claim 1, wherein the groups represented by R6 when attached to carbon atom are substituted, the substituents may be selected from halogen, hydroxy, nitro or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aralkyl, aryloxy, aralkoxy, aralkoxyalkyl, heterocyclyl, heteroaryl, heteroaralkyl, alkanoyl, alkanoyloxy; hydroxyalkyl, amino, acylamino, arylamino, aminoalkyl, alkoxycarbonyl, alkylamino, alkoxyalkyl, alkylthio, thioalkyl groups, carboxylic acid or its derivatives or sulfonic acid or its derivatives.

4. A compound of formula (I) according to claim 1, wherein Ar represents substituted or unsubstituted divalent phenylene, naphthylene, pyridyl, quinolinyl, benzofuryl, dihydrobenzofuryl, benzopyranyl, indolyl, indolinyl, azaindolyl, azaindolinyl, pyrazolyl, benzothiazolyl or benzoxazolyl groups.

5. A compound of formula (I) according to claim 1, wherein the groups represented by R6 when attached to nitrogen are substituted, preferred substituents may be selected from halogens hydroxy, alkanoyl, alkanoyloxy, amino groups.

6. A compound of formula (I) according to claim 1, wherein the groups represented by R7 and R8 attached to carbon atom are substituted, the substituent may be selected from halogen, hydroxy, nitro or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aralkyl, aryloxy, aralkoxy, aralkoxyalkyl, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, arylamino, aminoalkyl, alkylamino, alkoxyalkyl, alkylthio, thioalkyl groups, carboxylic acid or sulfonic acid.

7. A compound of formula (I) according to claim 1, wherein the groups represented by R7 and R8 when attached to nitrogen are substituted, preferred substituents may be selected from halogen such as fluorine, chlorine; hydroxy, alkyl, alkanoyl, alkanoyloxy or amino groups.

8. A process for the preparation of compound of formula (I) its derivatives, its analogs, its tautomeric forms, its stereoisomers, its polymorphs, its pharmaceutically acceptable salts, its pharmaceutically acceptable solvates, where R1 forms a bond together with the adjacent group R2; R3 may be hydrogen atom or substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, alkanoyl, aroyl, aralkyl, heterocyclyl, heteroaryl, heteroaralkyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbouyl, aiylaminocarbonyl groups, with a provision that R3 does not represent hydrogen when R4 represents hydrogen or lower alkyl group; R4 may be hydrogen or substituted or unsubstititted groups selected from alkyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl or heteroaralkyl groups; Y
represents oxygen; n is an integer ranging from 1- 4; Ar represents substituted or unsubstituted, divalent, single or fused, aromatic or heterocyclic group; A
represents a cyclic structure given below where X represents O or S; R6 when attached to the carbon atom represents hydrogen, halogen, hydroxy, nitro, cyano, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heterbaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, acylamino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R6 when attached to nitrogen atom represents hydrogen, hydroxy, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aralkyl, aryloxy, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl groups, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R7 and R8 when attached to carbon atom may be same or different and represent hydrogen, halogen, hydroxy, cyano, nitro, formyl or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxyalkyl, thioalkyl, alkylthio groups;
R7 and R8 when attached to nitrogen may be same or different and represent hydrogen, hydroxy or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino groups, which comprises:
a) reacting a compound of formula (IIIa) A-(CH2)n O-Ar-CHO (IIIa) where all symbols are as defined above with a compound of formula (IIIb) where R9 represents (C1-C6)alkyl and all other symbols are as defined above, to yield the compound of general formula (I) where all symbols are as defined above;
b) reacting the compound of formula (IIIa) A-(CH2)n O-Ar-CHO (IIIa) where all symbols are as defined above with Wittig reagent to yield a compound of formula (I) where all symbols are as defined above;
(c) reacting a compound of formula (IIIc) A-H (IIIc) where A is as defined above with a compound of formula (IIId) where R1, R2 together represent a bond and all other symbols are as defined above and L1 is a leaving group to produce a compound of general formula (I) defined above;
d) reacting a compound of formula (IIIa) A-(CH2)n O=Ar-CHO (IIIa) where all symbols are as defined above, with compound of formula (IIIe) where R2 represents hydrogen atom and all other symbols are as defined above to produce a compound of the formula (I) defined above;
e) reacting a compound of formula (IIIg) A-(CH2)n-L1 (IIIg) where A and n are as defined above and L1 represents a leaving group, with compound of formula (IIIf) where R1 and R2 together represent a bond and all other symbols are as defined above to produce a compound of the formula (I) defined above;
f) reacting a compound of formula (IIIh) A-(CH2)n OH (IIIh) where A and n symbols are as defined above with a compound of general formula (IIIf) where R1 and R2 together represent a bond and all other symbols are as defined above to produce a compound of formula (I) defined above;
g) reacting a compound of formula (IIIi) A-(CH2)n O-Ar-CH2-PPh3Hal- (IIIi) where Hal represents halogen arid A, Ar and n are as defined above with a compound of formula (IIIj) where R3 = R4 and are as defined above excluding hydrogen to produce a compound of the formula (I);
h) converting the compounds of formula (I) obtained in any of the processes described above into pharmaceutically acceptable salts or pharmaceutically acceptable solvates by conventional methods.

9. A process for the preparation of compound of formula (I) its derivatives, its analogs, its tautomeric forms, its stereoisomers, its polymorphs, its pharmaceutically acceptable salts, its pharmaceutically acceptable solvates, where R1 represents hydrogen atom, halogen, hydroxy, lower alkyl, alkoxy, substituted or unsubstituted aralkyl group; R2 represents hydrogen, hydroxy, halogen, lower alkyl, alkoxy, alkanoyl, aroyl aralkanoyl;
substituted or unsubstituted aralkyl group; R3 may be hydrogen atom or substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, alkanoyl, aroyl, aralkyl, heterocyclyl, heteroaryl, heteroaralkyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl groups, with a provision that R3 does not represent hydrogen when R4 represents hydrogen or lower alkyl group; R4 may be hydrogen or substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl or heteroaralkyl groups; Y represents oxygen; n is an integer ranging from 1- 4; Ar represents substituted or unsubstituted, divalent, single or fused, aromatic or heterocyclic group; A represents a cyclic structure given below:
where X represents O or S; R6 when attached to the carbon atom represents hydrogen, halogen, hydroxy, nitro, cyano, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, acylamino, monoalkylamino, dialkylamino, arylamino; aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R6 when attached to nitrogen atom represents hydrogen, hydroxy, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aralkyl, aryloxy, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy; hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl groups, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R7 and R8 when attached to carbon atom may be same or different and represent hydrogen, halogen, hydroxy, cyano, nitro, formyl or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxyalkyl, thioalkyl, alkylthio groups;
R7 and R8 when attached to nitrogen may be same or different and represent hydrogen, hydroxy or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino groups, which comprises a) reducing methods a compound of formula (IVa) which represents a compound of formula (I) where R1 and R2 together represent a bond and Y represent oxygen atom and all other symbols are as defined above, to yield a compound of the general formula (I) wfere R1 and R2 each represent hydrogen atom and all other symbols are as defined above;
b) reacting a compound of formula (IVb) where R4 is as defined above excluding hydrogen, L3 is a leaving group and all other symbols are as defined above and with an alcohol of general formula (IVc), R3OH (IVc) where R3 represents substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, aralkyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkanoyl, aroyl, heterocyclyl, heteroaryl, heteroaralkyl groups to produce a compound of the formula (I) defined above;
c) reacting a compound of formula (IIIg) A-(CH2)n-L1 (IIIg) where L1 is a leaving group and A, n are as defined above with a compound of formula (IIIf) where all symbols are as defined above to produce a compound of the formula (I) defined above;
d) reacting a compound of formula (IIIh) A-(CH2)n-OH (IIIh) where A and n are as defined above with a compound of general formula (IIIf) where all symbols are as defined above to produce a compound of the formula (I) defined above;
e) reacting a compound of formula (IVd) which represents a compound of formula (I) where R3 represent hydrogen atom and all symbols are as defined above with a compound of formula (IVe) R3-L3 (IVe) where R3 represents substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, aralkyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkanoyl, aroyl, heterocyclyl, heteroaryl, heteroaralkyl groups and L3 is a halogen atom to produce a compound of formula (I) defined above;
f) reacting a compound of the formula (IIIa) A-(CH2)n O-Ar-CHO (IIIa) where all symbols are as defined above with a compound of formula (IIIe) where R2 is hydrogen and all other symbols are as defined above to yield a compound of formula (I) as defined above after dehydroxylation;
g) reacting a compound of general formula (IIIc) A-H (IIIc) where A is as defined above with a compound of formula (IIId) where L1 is a leaving group, and all other symbols are as defined above to produce a compound of general formula (I) defined above;
h) converting a compound of formula (IVf) where all symbols are as defined above to a compound of formula (I) defined above;
i) reacting a compound of formula (IVg) where R4 is as defined above excluding hydrogen and all other symbols as defined above with a compound of formula (IVc) R3OH (IVc) where R3 represents substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, aralkyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkanoyl, aroyl, heterocyclyl, heteroaryl, heteroaralkyl groups to produce a compound of formula (I);
j) converting the compounds of formula (I) obtained in any of the processes described above into pharmaceutically acceptable salts or pharmaceutically acceptable solvates by conventional methods.

10. A process for the preparation of compound of formula (I) its derivatives, its analogs, its tautomeric forms, its stereoisomers, its polymorphs, its pharmaceutically acceptable salts, its pharmaceutically acceptable solvates, where R1 represents hydrogen atom, halogen, hydroxy, lower alkyl, alkoxy, substituted or unsubstituted aralkyl group or forms a bond together with the adjacent group R2; R2 represents hydrogen, hydroxy, halogen, lower alkyl, alkoxy, alkanoyl, aroyl, aralkanoyl, substituted or unsubstituted aralkyl or R2 forms a bond together with R1; R3 may be hydrogen atom or substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, alkanoyl, aroyl, aralkyl, heterocyclyl, heteroaryl, heteroaralkyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl groups, with a provision that R3 does not represent. hydrogen when R4 represents hydrogen; Y represents oxygen; n is an integer ranging from 1- 4; Ar represents substituted or unsubstituted, divalent, single or fused, aromatic or heterocyclic group; A represents a cyclic structure given below:
where X represents O or S; R6 when attached t6 the carbon atom represents hydrogen, halogen, hydroxy, nitro, cyano, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, acylamino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R6 when attached to nitrogen atom represents hydrogen, hydroxy, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aralkyl, aryloxy, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl groups, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R7 and R8 when attached to carbon atom may be same or different and represent hydrogen, halogen, hydroxy, cyano, nitro, formyl or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxyalkyl, thioalkyl alkylthio groups;
R7 and R8 when attached to nitrogen may be same or different and represent hydrogen, hydroxy or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino groups, which comprises a hydrolysing a compound of formula (I) described in any of the claim 8, where R4 represents substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl, heteroaralkyl groups and all other symbols are as defined earlier by conventional methods.

11. A process for the preparation of compound of formula (I) its derivatives, its analogs, its tautomeric forms, its stereoisomers, its polymorphs, its pharmaceutically acceptable salts, its pharmaceutically acceptable solvates, where where R1 represents hydrogen atom, halogen, hydroxy, lower alkyl, alkoxy, substituted or unsubstituted aralkyl group or forms a bond together with the adjacent group R2; R2 represents hydrogen, hydroxy, halogen, lower alkyl, alkoxy, alkanoyl, aroyl, aralkanoyl, substituted or unsubstituted aralkyl or R2 forms a bond together with R1; R3 may be hydrogen atom or substituted or unsubstituted groups selected from alkyl, cycloalkyl; aryl, alkanoyl, aroyl, aralkyl, heterocyclyl, heteroaryl, heteroaralkyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl groups, with a provision that R3 does not represent hydrogen when R4 represents hydrogen; Y represents oxygen; n is an integer ranging from 1- 4; Ar represents substituted or unsubstituted, divalent, single or fused, aromatic or heterocyclic group; A represents a cyclic structure given below:

where X represents O or S; R6 when attached to the carbon atom represents hydrogen, halogen, hydroxy, vitro, cyano, formyl or substituted or unsubstituted groups selected from a alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, acylamino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R6 when attached to nitrogen atom represents hydrogen, hydroxy, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aralkyl, aryloxy, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl groups, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R7 and R8 when attached to carbon atom may be same or different and represent hydrogen, halogen, hydroxy, cyano, nitro, formyl or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxyalkyl, thioalkyl, alkylthio groups;
R7 and R8 when attached to nitrogen may be same or different and represent hydrogen, hydroxy or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino groups, which comprises : hydrolysing a compound of formula (I) described in any of the claim 9, where R4 represents substituted or unsubstituted groups selected from alkyl cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl, heteroaralkyl groups and all other symbols are as defined earlier by conventional methods.

12. A process for the preparation of compound of formula (I) its derivatives, its analogs, its tautomeric forms, its stereoisomers, its polymorphs, its pharmaceutically acceptable salts, its pharmaceutically acceptable solvates, where R1 represents hydrogen atom, halogen, hydroxy, lower alkyl, alkoxy, substituted or unsubstituted aralkyl group or forms a bond together with the adjacent group R2; R2 represents hydrogen, hydroxy, halogen, lower alkyl, alkoxy, alkanoyl, aroyl, aralkanoyl, substituted or unsubstituted aralkyl or R2 forms a bond together with R1; R3 may be hydrogen atom or substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, alkanoyl, aroyl, aralkyl, heterocyclyl, heteroaryl, heteroaralkyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl groups, with a provision that R3 does not represent hydrogen when R4 represents hydrogen or lower alkyl group; R4 may be hydrogen or substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl or heteroaralkyl groups; Y
represents NR5, where R5 represents hydrogen or substituted or unsubstituted groups selected from alkyl, aryl, aralkyl, hydroxyalkyl, alkanoyl, aroyl, aralkanoyl, heterocyclyl, heteroaryl, or heteroaralkyl groups; R4 and R5 together may form a substituted or unsubstituted 5 or 6 membered cyclic structure containing carbon atoms, a nitrogen atom and which may optionally contain one or more additional heteroatoms selected from oxygen, sulfur or nitrogen; n is an integer ranging from 1- 4; Ar represents substituted or unsubstituted, divalent, single or fused, aromatic or heterocyclic group; A
represents a cyclic structure given below:

where X represents O or S; R6 when attached to the carbon atom represents hydrogen, halogen, hydroxy, nitro, cyano, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, acylamino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R6 when attached to nitrogen atom represents hydrogen, hydroxy, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aralkyl, aryloxy, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl groups, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R7 and R8 when attached to carbon atom may be same or different and represent hydrogen, halogen, hydroxy, cyano, nitro, formyl or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxyalkyl, thioalkyl, alkylthio groups;
R7 and R8 when attached to nitrogen may be same or different and represent hydrogen, hydroxy or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino groups, which comprises:
a) reacting a compound of formula (I) where all symbols are as defined above and Y represent oxygen or YR4 represents a halogen atom or COYR4 represents a mixed anhydride group with appropriate amines of the formula NHR4R5, where R4 and R5 are as defined earlier and if desired;
b) converting the compounds of formula (I) obtained above into pharmaceutically acceptable salts or pharmaceutically acceptable solvates by conventional methods.

13. A compound of formula (I) its derivatives, its analogs, its tautomeric forms, its stereoisomers, its polymorphs, its pharmaceutically acceptable salts, its pharmaceutically acceptable solvates, where R1 forms a bond together with the adjacent group R2; R3 may be hydrogen atom or substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, alkanoyl, aroyl, aralkyl, heterocyclyl, heteroaryl, heteroaralkyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl groups, with a provision that R3 does not represent hydrogen when R4 represents hydrogen or lower alkyl group; R4 may be hydrogen or substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl or heteroaralkyl groups; Y
represents oxygen; n is an integer ranging from 1- 4; Ar represents substituted or unsubstituted, divalent, single or fused, aromatic or heterocyclic group; A
represents a cyclic stricture given below:

where X represents O or S; R6 when attached to the carbon atom represents hydrogen, halogen, hydroxy, nitro, cyano, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy; hydroxyalkyl, amino, acylamino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R6 when attached to nitrogen atom represents hydrogen, hydroxy, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aralkyl, aryloxy, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl groups, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R7 and R8 when attached to carbon atom may be same or different and represent hydrogen, halogen, hydroxy, cyano, nitro, formyl or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxyalkyl, thioalkyl, alkylthio groups;
R7 and R8 when attached to nitrogen may be same or different and represent hydrogen, hydroxy or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino groups, prepared according to the process of claim 8.

14. A compound of formula (I) its derivatives, its analogs, its tautomeric forms, its stereoisomers, its polymorphs, its pharmaceutically acceptable salts, its pharmaceutically acceptable solvates, where R1 represents hydrogen atom, halogen, hydroxy, lower alkyl, alkoxy, substituted or unsubstituted aralkyl group; R2 represents hydrogen, hydroxy, halogen, lower alkyl, alkoxy, alkanoyl, aroyl, aralkanoyl, substituted or unsubstituted aralkyl group; R3 may be hydrogen atom or substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, alkanoyl, aroyl, aralkyl, heterocyclyl, heteroaryl, heteroaralkyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl groups, with a provision that R3 does not represent hydrogen when R4 represents hydrogen or lower alkyl group; R4 may ba hydrogen or substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl or heteroaralkyl groups; Y represents oxygen; n is an integer ranging from 1- 4; Ar represents substituted or unsubstituted, divalent, single or fused, aromatic or heterocyclic group; A represents a cyclic structure given below:

where X represents O or S; R6 when attached to the carbon atom represents hydrogen, halogen, hydroxy, nitro, cyano, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, acylamino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R6 when attached to nitrogen atom represents hydrogen, hydroxy, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aralkyl, aryloxy, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl; alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl groups, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R7 and R8 when attached to carbon atom may be same or different and represent hydrogen, halogen, hydroxy, cyano, nitro, formyl or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxyalkyl, thioalkyl, alkylthio groups;
R7 and R8 when attached to nitrogen, may be same or different and represent hydrogen, hydroxy or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino groups, prepared according to the process of claim 9.

15. A compound of formula (I) its derivatives, its analogs, its tautomeric forms, its stereoisomers, its polymorphs, its pharmaceutically .acceptable salts, its pharmaceutically acceptable solvates, where R1 represents hydrogen atom, halogen, hydroxy, louver alkyl, alkoxy, substituted or unsubstituted aralkyl group or forms a bond together with the adjacent group R2; R2 represents hydrogen, hydroxy, halogen, lower alkyl, alkoxy, alkanoyl, aroyl, aralkanoyl, substituted or unsubstituted aralkyl or R2 forms a bond together with R1; R3 may be hydrogen atom or substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, alkanoyl, amyl, aralkyl, heterocyclyl, heteroaryl, heteroaralkyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl groups, with a provision that R3 does not represent hydrogen when R4 represents hydrogen; Y represents oxygen; n is an integer ranging from 1- 4; Ar represents substituted or unsubstituted, divalent, single or fused, aromatic or heterocyclic group; A represents a cyclic structure given below:

where X represents O or S; R6 when attached to the carbon atom represents hydrogen, halogen, hydroxy, nitro, cyano, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, acylamino, monoalkylamino, dialkylamino, arylamino, aralkylamino,-aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R6 when attached to nitrogen atom represents hydrogen, hydroxy, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aralkyl, aryloxy, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl groups, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R7 and R8 when attached to carbon atom may be same or different and represent hydrogen, halogen, hydroxy, cyano, nitro, formyl or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxyalkyl, thioalkyl, alkylthio groups;
R7 and R8 when attached to nitrogen may be same or different and represent hydrogen, hydroxy or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino groups, groups prepared according to the process of claim 10.

16. A compound of formula (I) its derivatives, its analogs, its tautomeric forms, its stereoisomers, its polymorphs, its pharmaceutically acceptable salts, its pharmaceutically acceptable solvates, where where R1 represents hydrogen atom, halogen, hydroxy, lower alkyl, alkoxy, substituted or unsubstituted aralkyl group or forms a bond together with the adjacent group R2; R2 represents hydrogen, hydroxy, halogen, lower alkyl, alkoxy, alkanoyl, aroyl, aralkanoyl, substituted or unsubstituted aralkyl or R2 forms a bond together with R1; R3 may be hydrogen atom or substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, alkanoyl, aroyl, aralkyl, heterocyclyl, heteroaryl, heteroaralkyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl groups, with a provision that R3 does not represent hydrogen when R4 represents hydrogen; Y represents oxygen; n is an integer ranging from 1- 4; Ar represents substituted or unsubstituted, divalent, single or fused, aromatic or heterocyclic group; A represents a cyclic structure given below:

where X represents O or S; R6 when attached to the carbon atom represents hydrogen, halogen, hydroxy, nitro, cyano, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, acylamino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R6 when attached to nitrogen atom represents hydrogen, hydroxy, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl; alkoxy, cycloalkoxy, aryl, aralkyl, aryloxy, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl groups, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R7 and R8 when attached to carbon atom may be same or different and represent hydrogen, halogen, hydroxy, cyano, nitro, formyl or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxyalkyl, thioalkyl, alkylthio groups;
R7 and R8 when attached to nitrogen may be same or different and represent hydrogen, hydroxy or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino groups, prepared according to the process of claim 11.

17. A compound of formula (I) its derivatives, its analogs, its tautomeric forms, its stereoisomers, its polymorphs, its pharmaceutically acceptable salts, its pharmaceutically acceptable solvates, where R1 represents hydrogen atom, halogen, hydroxy, lower alkyl, alkoxy, substituted or unsubstituted aralkyl group or forms a bond together with the adjacent group R2; R2 represents hydrogen, hydroxy, halogen, lower alkyl, alkoxy, alkanoyl, aroyl, aralkanoyl, substituted or unsubstituted aralkyl or R2 forms a bond together with R1; R3 may be hydrogen atom or substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, alkanoyl, amyl, aralkyl, heterocyclyl, heteroaryl, heteroaralkyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl groups, with a provision that R3 does not represent hydrogen when R4 represents hydrogen or lower alkyl group; R4 may be hydrogen or substituted or unsubstituted groups selected from alkyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl or heteroaralkyl groups; Y
represents NR5, where R5 represents hydrogen or substituted or unsubstituted groups selected from alkyl, aryl, aralkyl, hydroxyalkyl, alkanoyl, aroyl, aralkanoyl, heterocyclyl, heteroaryl or heteroaralkyl groups; R4 and R5 together may form a substituted or unsubstituted 5 or 6 membered cyclic structure containing carbon atoms, a nitrogen atom and which may optionally contain one or more additional heteroatoms selected from oxygen, sulfur or nitrogen; n is an integer ranging from 1- 4; Ar represents substituted or unsubstituted, divalent, single or fused, aromatic or heterocyclic group; A
represents a cyclic structure given below:

where X represents O or S; R6 when attached to the carbon atom represents hydrogen, halogen, hydroxy, nitro, cyano, formyl or substituted or unsubstituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, acylamino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkoxycarbonylamino, aryloxycarbonylamino, aralkoxycarbonylamino, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R6 when attached to nitrogen atom represents hydrogen, hydroxy, formyl or substituted or W substituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aralkyl, aryloxy, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, alkanoyl, aroyl, alkanoyloxy, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl groups, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R7 and R8 when attached to carbon atom may be same or different and represent hydrogen, halogen, hydroxy, cyano, nitro, formyl or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino, aralkylamino, aminoalkyl, alkoxyalkyl, thioalkyl, alkylthio groups;
R7 and R8 when attached to nitrogen may be same or different and represent hydrogen, hydroxy or substituted or unsubstituted groups selected from alkyl, alkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, hydroxyalkyl, amino, monoalkylamino, dialkylamino, arylamino groups, prepared according to the process of claim 12.

18. A compound according to claim 1, which is selected from (~) Ethyl 2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoate (+) Ethyl 2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoate;

(-) Ethyl 2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoate;

(~) 2-Ethoxy 3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoic acid or its salts;

(+) 2-Ethoxy 3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoic acid or its salts;

(-) 2-Ethoxy 3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoic acid or its salts ;

(~) Ethyl 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate ;

(+) Ethyl 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate ;

(-) Ethyl 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate ;

(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its salts;

(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its salts;

(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its salts ;

(~) Ethyl 2-ethoxy-3-[4-[2-(1-methyl-7-oxo-3-propyl-5-trifluoromethyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoate ;

(+) Ethyl 2-ethoxy-3-[4-[2-(1-methyl-7-oxo-3-propyl-5-trifluoromethyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoate ;

(-) Ethyl 2-ethoxy-3-[4-[2-(1-methyl-7-oxo-3=propyl-5-trifluoromethyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoate ;

(~) Ethyl 3-[4-[2-(5-benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate ;

(+) Ethyl 3-[4-[2-(5-benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate ;

(-) Ethyl 3-[4-[2-(5-benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate ;

(~) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its salts;

(+) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its salts;

(-) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its salts;

(~) Ethyl 3-[4-[2-(5-benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;

(+) Ethyl 3-[4-[2-(5-benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;

(-) Ethyl 3-[4-[2-(5-benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;

(~) Ethyl 3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;

(+) Ethyl 3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;

(-) Ethyl 3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;

(~) 3-[4-[2-(5-Ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts;

(+) 3-[4-[2-(5-Ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts;

(-) 3-[4-[2-(5-Ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts ;

(~) Ethyl 3-[4-[2-(1,5-dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;

(+) Ethyl 3-[4-[2-(1,5-dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;

(-) Ethyl 3-[4-[2-(1,5-dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate;

(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts ;

(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts;

(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts ;

(~) Ethyl 3-[4-[2-(3,5-dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate ;

(+) Ethyl 3-[4-[2-(3,5-dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate ;

(-) Ethyl 3-[4-[2-(3,5-dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoate ;

(~) 3-[4-[2-(3,5-Dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its salts;

(+) 3-[4-[2-(3,5-Dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its salts;

(-) 3-[4-[2-(3,5-Dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its salts;

(~) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts;

(+) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts;

(-) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts;

(~) Ethyl 3-[4-[2-(3,5-dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;

(+) Ethyl 3-[4-[2-(3,5-dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoate ;

(-) Ethyl 3-[4-[2-(3,5-dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2,-phenoxypropanoate ;

(~) 3-[4-[2-(3,5-Dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts ;

(+) 3-[4-[2-(3,5-Dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts ;

(-) 3-[4-[2-(3,5-Dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its salts;

[2R, N(1S)]-2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-y]ethoxy]phenyl]-N-(2-hydroxy-1-phenylethyl)propanamide and [2S, N(1S)]-2-ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-y]ethoxy]phenyl]-N-(2-hydroxy-1-phenylethyl)propanamide.

19. A compound according to claim 1 wherein the pharmaceutically acceptable salt is selected from L,i, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts.

20. A compound according to claim 18, which is selected from:

(~) 2-Ethoxy 3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-67-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts ;

(+) 2-Ethoxy 3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4a3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts ;

(-) 2-Ethoxy 3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]propanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts ;

(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts ;

(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts ;

(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid, or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts ;

(~) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, chore, ammonium, substituted ammonium salts or aluminium salts ;

(+) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammoniuriysalts or aluminium salts ;

(-) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts ;

(~) 3-[4-[2-(5-Ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts ;

(+) 3-[4-[2-(5-Ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its Li, Na, K, Cap (~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts ;

(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts ;

(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its Li, Na, K, Ca, Mg, lysine arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts ;

(~) 3-[4-[2-(3,5-Dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts ;

(+) 3-[4-[2-(3,5-Dipropyl-1=methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts ;

(-) 3-[4-[2-(3;5-Dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts;

(~) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its Li, Na, K;

Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts ;

(+) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts ;

(-) 3-[4-[2-(5-Benzyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts ;

(~) 3-[4-[2-(3,5-Dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts ;

(+) 3-[4-[2-(3,5-Dipropyl-1-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline, ammonium, substituted ammonium salts or aluminium salts and (-) 3-[4-[2-(3,5-Dipropyl-1-methyl-7-oxo-6;7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-phenoxypropanoic acid or its Li, Na, K, Ca, Mg, lysine, arginine, guanidine, diethanolamine, choline; ammonium, substituted ammonium salts or aluminium salts.

21. A pharmaceutical composition, which comprises a compound of formula (I) as defined in claim 1 and a pharmaceutically acceptable carrier, diluent, excipient or solvate.

22. A pharmaceutical composition as claimed in claim 21, in the form of a tablet, capsule, powder, syrup, solution or suspension.

23, A method of preventing or treating hyperlipemia, hypercholesteremia, hyperglycemia, osteoporosis, obesity, glucose intolerance, leptin resistance, insulin resistance, or diseases in which insulin resistance is the underlying pathophysiological mechanism comprising administering a compound of formula (I) as defined in claim 1 or a pharmaceutical composition as claimed in claims 21 and 22 to a patient in need thereof.

24. A method according to claim.23, wherein the,disease is type II diabetes, impaired glucose tolerance, dyslipidaemia, disorders related to Syndrome X
such as hypertension, obesity, atherosclerosis, hyperlipidemia, coronary artery disease and other cardiovascular disorders, certain renal diseases including glomerulonephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis, retinopathy, nephropathy, disorders related to endothelial cell activation, psoriasis, polycystic ovarian syndrome (PCOS), useful as aldose reductase inhibitors, for improving cognitive functions in dementia and treating diabetic complications, osteoporosis, inflammatory bowel diseases, myotonic dystrophy, pancreatitis, arteriosclerosis, xarithorria and cancer.

25. A method for the treatment and / or prophylaxis of disorders related to Syndrome X, which comprises administering an effective amount of an agonist of PPAR.alpha. and / or PPAR.gamma. of formula (I) to a patient in need thereof.

26. A method of reducing plasma glucose, triglycerides; total cholesterol, LDL, VLDL and free fatty acids in the plasma comprising administering an effective amount of a compound of formula (I) as defined, in claim 1 to a patient in need thereof

27. A method according to claim 23 wherein a compound of formula (I) administered in combination / concoimittant with HMG CoA reductase inhibitors or fibrates or nicotinic acid or cholestyramine or colestipol or probucol which may be administered together or within such a period as to act synergistically together to a patient in need thereof.

28. A method according to claim 23, wherein a composition as defined in claim 21 is administered in combination / concomittant with HMG CoA
reductase inhibitors or fibrates or nicotinic acid or cholestyramine or colestipol or probucol which may be administered together or within such a period as to act synergistically together to a patient in need thereof.

29. A method according to claim 24, wherein a compound of formula (I) administered in combination / concomittant with HMG CoA reductase inhibitors or fibrates or nicotinic acid or cholestyramine or colestipol or probucol which may be administered together or within such a period as to act synergistically together to a patient in need thereof.

30. A method according to claim 25, wherein a compound of formula (I) administered in combination / concomittant with HMG CoA reductase inhibitors or fibrates or nicotinic acid or cholestyramine or colestipol or probucol which may be administered together or within such a period as to act synergistically together to a patient in need thereof.

31. A method of reducing plasma glucose, triglycerides, total cholesterol, LDL, VLDL and free fatty acids in the plasma comprising administering an effective amount of a compound of formula (I) as defined in claim 1 in combination / concomittant with HMG CoA reductase inhibitors or fibrates or nicotinic acid or cholestyramine or colestipol or probucol which may be administered together or within such a period as to act synergistically together to a patient in need thereof.

32. A pharmaceutical composition which comprises a compound as claimed in claim 18 and a pharmaceutically acceptable carrier, diluent, excipient or solvate.

33. A pharmaceutical composition as claimed in claim 32, in the form of a tablet, capsule, powder, syrup, solution or suspension.

34. A pharmaceutical composition which comprises a compound as claimed in claim 20 and a pharmaceutically acceptable carrier, diluent, excipient or solvate.

35. A pharmaceutical composition as claimed in claim 34, in the form of a tablet, capsule, powder, syrup, solution or suspension.

36. A method of preventing or treating hyperlipemia, hypercholesteremia, hyperglycemia, osteoporosis, obesity, glucose intolerance, leptin resistance, insulin resistance, or diseases in which insulin resistance is the underlying pathophysiological mechanism comprising administering a compound of formula (I) as defined in claim 1 or a pharmaceutical composition as claimed in claim 18 to a patient in need thereof.

37. A method according to claim 36, wherein the, disease is type II diabetes, impaired glucose tolerance, dyslipidaemia, disorders related to Syndrome X
such as hypertension, obesity, atherosclerosis, hyperlipidemia, coronary artery disease and other cardiovascular disorders, certain renal diseases including glomerulonephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis, retinopathy, nephropathy, disorders related to endothelial cell activation, psoriasis, polycystic ovarian syndrome (PCOS), useful as aldose reductase inhibitors, for improving cognitive functions in dementia and treating diabetic complications, osteoporosis, inflammatory bowel diseases, myotonic dystrophy, pancreatitis, arteriosclerosis xanthoma and cancer.

38. A method for the treatment and / or prophylaxis of disorders related to Syndrome X, which comprises administering an effective amount of an agonist of PPAR.alpha. and / or PPAR.gamma. of formula (I) as claimed in claim 18 to a patient in need thereof.

39. A method of reducing plasma glucose, triglycerides, total cholesterol, LDL, VLDL and free fatty acids in the plasma comprising administering an effective amount of a compound of formula (I) as defined in claim 18 to a patient in need thereof

40. A method according to claim 36 wherein a compound of formula (I) administered in combination / concomittant with HMG CoA reductase inhibitors or filtrates or nicotinic acid or cholestyramine or colestipol or probucol which may be administered together or within such a period as to act synergistically together to a patient in need thereof.

41. A method according to claim 37, wherein a compound of formula (I) is administered in combination / concomittant with HMG CoA reductase inhibitors or fibrates or nicotinic acid or cholestyramine or colestipol or probucol which may be administered together or within such a period as to act synergistically together to a patient in need thereof.

42. A method according to claim 38, wherein a compound of formula (I) administered in combination / concomittant with HMG CoA reductase inhibitors or fibrates or nicotinic acid or cholestyramine or colestipol or probucol which may be administered together or within such a period as to act synergistically together to a patient in need thereof.

43. A method of reducing plasma glucose, triglycerides, total cholesterol, LDL, VLDL and free fatty acids in the plasma comprising administering an effective amount of a compound of formula (I) as defined in claim 18 in combination / concomittant with HMG CoA reductase inhibitors or fibrates or nicotinic acid or cholestyramine or colestipol or probucol which may be administered together or within such a period as to act synergistically together to a patient in need thereof.

44. A method of preventing or treating hyperlipemia, hypercholesteremia, hyperglycemia, osteoporosis, obesity, glucose intolerance, leptin resistance, insulin resistance, or diseases in which insulin resistance is the underlying pathophysiological mechanism comprising administering a compound of formula (I) as defined in claim 1 or a pharmaceutical composition as claimed in claim 20 to a patient in need thereof.

45. A method according to claim 44, wherein the disease is type II diabetes, impaired glucose tolerance, dyslipidaemia, disorders related to Syndrome X
such as hypertension, obesity, atherosclerosis, hyperlipidemia, coronary artery disease and other cardiovascular disorders, certain renal diseases including glomerulonephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis, retinopathy, nephropathy, disorders related to endothelial cell activation, psoriasis, polycystic ovarian syndrome (PCOS), useful as aldose reductase inhibitors, for improving cognitive functions in dementia and treating diabetic complications, osteoporosis, inflammatory bowel diseases, myotonic dystrophy, pancreatitis, arteriosclerosis, xanthoma and cancer.

46. A method for the treatment and / or prophylaxis of disorders related to Syndrome X, which comprises administering an effective amount of an agonist of PPAR.alpha. and / or PPAR.gamma. of formula (I) as claimed in claim 20 to a patient in need thereof.

47. A method of reducing plasma glucose, triglycerides, total cholesterol, LDL, VLDL and free fatty acids in the plasma comprising administering an effective amount of a compound of formula (I) as defined in claim 20 to a patient in need thereof

48. A method according to claim 44 wherein a compound of formula (I) administered in combination / concomittant with HMG CoA reductase inhibitors or fibrates or nicotinic acid or cholestyramine or colestipol or probucol which may be administered together or within such a period as to act synergistically together to a patient in need thereof.

49. A method according to claim 45, wherein the compound of formula (I) is administered in combination / concomittant with HMG CoA reductase inhibitors or fibrates or nicotinic acid or cholestyramine or colestipol or probucol which may be administered together or within such a period as to act synergistically together to a patient in need thereof.

50. A method according to claim 46, wherein a compound of formula (I) administered in combination / concomittant with HMG CoA reductase inhibitors or fibrates or nicotinic acid or cholestyramine or colestipol or probucol which may be administered together or within such a period as to act synergistically together to a patient in need thereof.

51. A method of reducing plasma glucose, triglycerides, total cholesterol, LDL, VLDL and free fatty acids in the plasma comprising administering an effective amount of a compound of formula (I) as defined in claim 20 in combination / concomittant with HMG CoA reductase inhibitors or fibrates or nicotinic acid or cholestyramine or colestipol or probucol which may be administered together or within such a period as to act synergistically together to a patient in need thereof.

52. Use of a compound of formula (I) as defined in claim 1 or a compound as claimed in claim 18 or 20 or a pharmaceutical composition as claimed in claims 21 and 22 for preventing or treating hyperlipemia, hypercholesteremia, hyperglycemia, osteoporosis, obesity, impaired glucose tolerance, atherosclerosis, leptin resistance, insulin resistance, or diseases in which insulin resistance is the underlying pathophysiological mechanism.

53. Use of a compound according to claim 53, wherein the disease is type II diabetes, impaired glucose tolerance, dyslipidemia, disorders related to Syndrome X such as hypertension, obesity, insulin resistance, coronary artery disease and other cardiovascular disorders; certain renal diseases including glomerulonephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis, retinopathy, nephropathy, disorders related to endothelial cell activation, psoriasis, polycystic ovarian syndrome (PCOS), dementia, diabetic complications, osteoporosis, inflammatory bowel diseases, myotonic dystrophy, pancreatitis, arteriosclerosis, xanthoma, eating disorders, cancer or as inflammatory agents

54. Use of a compound of formula (I) as defined in claim in claim 1 or a compound as claimed in claim 18 or 20 or a pharmaceutical composition as claimed in claims 21 and 22 for reducing plasma glucose, triglycerides, total cholesterol, LDL, VLDL or free fatty acids or increasing HDL in the plasma.

55. Use of a compound of formula (I) as defined in claim in claim 1 or a compound as claimed in claim 18 or 20 or a pharmaceutical composition as claimed in claims 21 and 22 an agonist of PPAR.alpha. and / or PPAR.gamma. of formula (I) to a patient in need thereof.

56. Use of a compound of formula (I) as defined in claim 1 or a compound as claimed in claim 18 or 20 or a pharmaceutical composition as claimed in claims 21 and 22 in combination/concomittant with HMG CoA reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol which may be administered together or within such a period as to act synergistically together for preventing or treating hyperlipemia, hypercholesteremia, hyperglycemia, osteoporosis, obesity, impaired glucose tolerance, atherosclerosis, leptin resistance, insulin resistance, or diseases in which insulin resistance is the underlying pathophysiological mechanism to a patient in need thereof.

57. Use of a compound according to claim 56, wherein the disease is type II diabetes, impaired glucose tolerance, dyslipidemia, disorders related to Syndrome X such as hypertension, obesity, insulin resistance, coronary artery disease and other cardiovascular disorders; certain renal diseases including glomerulonephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis, retinopathy, nephropathy, disorders related to endothelial cell activation, psoriasis, polycystic ovarian syndrome (PCOS), dementia, diabetic complications, osteoporosis, inflammatory bowel diseases, myotonic dystrophy, pancreatitis, arteriosclerosis, xanthoma, eating disorders, cancer or as inflammatory agents.

58. Use of a compound of formula (I) as defined in claim in claim 1 or a compound as claimed in claim 18 or 20 or a pharmaceutical composition as claimed in claims 21 and 22 in combination/concomittant with HMG CoA
reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol for reducing plasma glucose, triglycerides, total cholesterol, LDL, VLDL or free fatty acids or increasing HDL in the plasma.

59. A medicine for preventing or treating hyperlipemia, hypercholesteremia, hyperglycemia, osteoporosis, obesity, impaired glucose tolerance, atherosclerosis, leptin resistance, insulin resistance, or diseases in which insulin resistance is the underlying pathophysiological mechanism comprising administering an effective amount of a compound of formula (I) as defined in claim 1 or a compound as claimed in claim 18 or 20 or a pharmaceutical composition as claimed in claims 21 and 22.

60. A medicine according to claim 59, wherein the disease is type II
diabetes, impaired glucose tolerance, dyslipidemia, disorders related to Syndrome X such as hypertension, obesity, insulin resistance, coronary artery disease and other cardiovascular disorders; certain renal diseases including glomerulonephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis, retinopathy, nephropathy, disorders related to endothelial cell activation, psoriasis, polycystic ovarian syndrome (PCOS), dementia, diabetic complications, osteoporosis, inflammatory bowel diseases, myotonic dystrophy, pancreatitis, arteriosclerosis, xanthoma, eating disorders, cancer or as inflammatory agents.

61. A medicine for reducing plasma glucose, triglycerides, total cholesterol, LDL, VLDL or free fatty acids or increasing HDL in the plasma comprising an effective amount of compound of formula (I) as defined in claim 1 or a compound as claimed in claim 18 or 20 or a pharmaceutical composition as claimed in claims 21 and 22.

62. A medicine for preventing or treating hyperlipemia, hypercholesteremia, hyperglycemia, osteoporosis, obesity, impaired glucose tolerance, atherosclerosis, leptin resistance, insulin resistance, or diseases in which insulin resistance is the underlying pathophysiological mechanism comprising a compound of formula (I) as defined in claim 1 or a compound as claimed in claim 18 or 20 or a pharmaceutical composition as claimed in claims 21 and 22 and HMG CoA reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol.

63. A medicine according to claim 62, wherein the disease is type II
diabetes, impaired glucose tolerance, dyslipidemia, disorders related to Syndrome X such as hypertension, obesity, insulin resistance, coronary artery disease and other cardiovascular disorders; certain renal diseases including glomerulonephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis, retinopathy, nephropathy, disorders related to endothelial cell activation, psoriasis, polycystic ovarian syndrome (PCOS), dementia, diabetic complications, osteoporosis, inflammatory bowel diseases, myotonic dystrophy, pancreatitis, arteriosclerosis, xanthoma, eating disorders, cancer or as inflammatory agents.

64. A medicine for reducing plasma glucose, triglycerides, total cholesterol, LDL, VLDL or free fatty acids or increasing HDL in the plasma, which comprises a compound of formula (I) claimed in claim 1 or a compound as claimed in claim 18 or 20 or a pharmaceutical composition as claimed in claims 21 and 22 and HMG CoA reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol.