CA2436738A1 - Salts of pyrimidine derivatives for use against coronary heart disease and atherosclerose - Google Patents

Abstract

The present invention relates to pharmaceutically acceptable salts of compou nd of the general formula (I), their derivatives, their analogs, their tautomer ic forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable solvates and pharmaceutically acceptable compositions containing them. The present invention relates to pharmaceutically acceptable salts of the general formula (I), their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs and pharmaceutically acceptable compositions containing them.

Description

pWAR.MACEUTICALLY ACCEPTABLE SALTS OF
HETEROCYCLIC COMPOUNDS
Field of the Invention The present invention relates. to pharmaceutically acceptable salts of compound of the general formula (I), their derivatives, their analogs, their tautomeria forms, their stereoisomersa their folymorphs, their pharmaceutically acceptable solvates and pharmaceutically acceptable compositions containing them.
~ a O
P
ORS p+
O M
The present invention also relates to a process for the preparation of the above said pharmaceutically acceptable salts, their derivatives, their analogs, their tautorrieric forms, their stereoisomersa their polymorphs, pharmiaceutically acceptable solvates, and pharmaceutical compositions containing them.
. The compounds of the present invention lower plasma glucose, triglycerides, lower total cholesterol (TC) and increase high density lipoprotein (HDL) and decrease low density lipoprotein (LDL)~ which have a beneficial effect on coronary heart disease and atherosclerosis.
The compounds of general formula (I) are useful in reducing body weight arid for the treatment andlor 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, VLI7L (very low density lipoprotein) and LI~L. The compounds of the present invention can be used for the treatment of certain renal diseases including CONFIRMATION COPY

glomerulonephritis, 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 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, treating diabetic complications, disorders related to endothelial cell activation, psoriasis, polycystic ovarian syndrome (PCOS), inflammatory bowel diseases, osteoporosis, myotoriic dystrophy, . pancreatitis, arteriosclerosis, retinopathy, xanthoina, eating disorders, inflammation and for the treatment of cancer. The compounds of the 'p'resent invention are also useful in the treatment and/or prophylaxis of the above said diseases in combination/concomittant with one or more HMG CoA reductase inhibitors, hypolipidemic/hypolipoproteinemic agents such as fabric acid derivatives, nicotinic acid, cholestyramine, colestipol and probucol.
Background of Invention Atherosclerosis and other peripheral vascular diseases effect the quality of life of millions of ,people. Therefore, considerable attention has been .
directed towards understanding the etiology of hypercholesterolemia and hyperlipiderizia and development of effective therapeutic strategies.
Hypercholesterolerilia has been defined as plasma cholesterol level that exceeds arbitrarily defined value called "normal" level. Recently, 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 Low density lipoprotein (LDL), Intermediate density lipoprotein (IDL), High 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 llPed., 325 (19'91), 373-381) and the risk of CAD increases with increasing levels of LDL and VLDL.
In CAD, generally "fatty streaks" in carotid, coronary and cerebral arteries, are found which are primarily free and esterified cholesterol.
Miller et al., (BY. Med. .7., 282 (1981), 1741 - 1744) have shown that increase in 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., A~tef°iosclerosis 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., J. Biol. them. 261 (1986), 2548 - 2552). Therefore, agents that increase HDL cholesterol would have therapeutic significance for the treatment of hypercholesterolemia 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 intake 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, 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 large population in the world. Insulin resistance is the S diminished ability of insulin to exert its biological action across a broad range 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 probleW Gild is associated with a variety of abnormalities including obesity, hypertension, hyperlipidemia (J. C'li~. IhvesB., 75 (1985) 809 - 817; N. Ehgl. J. lVled 317 (1987) 350-357; J. Clin. Endocrinol. Metab., 66 (1988) 580 e- 583; J. Clira.
Invest., 68 (1975) 957 - 969) and other renal complications (patent publication No. ~WO 95/21608). It is now increasingly being recognized that insulin resistance and relative hyperinsulinemia have a contributory role in obesity, hypertension, atherosclerosis and type 2 diabetes mellitus. The association of insulin resistance with obesity, hypertension and angina ha's been described as a syndrome haviilg insulin resistance as the central pathogenic link-Syndrome-X.
Hyperlipidemia is the primary cause for cardiovascular (CHID) and other peripheral vasculax diseases. High risk 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 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 nuclear receptor super family. The gamma (y) isoform of PPAR (PPARy) has S
been implicated in regulating differentiation of adipocytes (E~cdocrifaology, 135 (19'94) 798-800) and energy homeostasis (Cell, 83 (1995) 803-812), whereas the alpha (a) isofonn of PPAR (PPARa) mediates fatty acid oxidation (Trend. Ehdocrin. Metab., 4 (1993) 291-296) thereby resulting in reduction of circulating free fatty acid in plasma (Current Biol. 5 (1995) 618 -621). PPAI~a agonists have been found useful for the treatment of obesity (WO 97/36579). It has been recently disclosed that coW pounds which are agonists for both PPARa and PPARy are suggested to be useful for the treatment of syndrome X (WO 97/25042). Similar effect between the insulin sensitizes (PPARy agonist) and HMG C~A reductase inhibitor has been observed which may be useful for the treatment of atherosclerosis and xanthoma (EP 0 753 298).
It is known that PPARy plays an important role in adipocyte differentiation (Cell, 87 (1996) 377-389). Ligand activation of PPAR is sufficient to cause complete terminal differentiation (Cell, 79 (1994) 1147 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; CaYCifzoge~cesis, (1998), 1949-53; Proc. Natl. Acad. Sci., 94 (1997) 237-241) and inhibition of expression of prostate cancer tissue (Cancef~ Research 58 (1998) 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 intake and reduced energy expenditure and cause impaired glucose tolerance, type 2 diabetes, cardiovascular diseases and such other interrelated 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 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 leptin concentrations by improving the target cell response to leptin (WO 98/02159).
In our WO publication 99/08501 we have disclosed and described the novel compounds of the formula (II), N R~ O
i (CH2)n-WAr R5 z R3 YR7 Rg0 X
R1 .
R N
where X represents O or S ; the groups R1, R2 and group R3 when attached to the carbon atom, may be same or different and represent hydrogen, halogen, hydroxy, vitro, cyano, formyl or optionally substituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aryloxy, aralkyl, aralkoxy, heterocyclyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroaralkoxy, acyl, acyloxy, hydroxyalkyl, amino, acylamino, alkylamino, arylamino, aralkylamino, aminoalkyl, allcoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioalkyl, alkoxycarbonylamino, aryloxycarbonylamilio, aralkoxycarbonylamino, carboxylic acid or its derivatives, or sulfonic acid or its derivatives; R1, R2 along with the adjacent atoms to which they are attached may also form a substituted or unsubstituted 5-6 meinbered 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 alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aralkyl, heterocyclyl, heteroaryl, heteroaralkyl, acyl, acyloxy, ' hydroxyalkyl, amino, acylamino, alkylamino, arylamino, aralkylamino, aW inoalkyl, aryloxy, arallcoxy, heteroaryloxy, heteroaralkoXy, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkoxyalkyl, aryloxyalkyl, aralkoxyalkyl, alkylthio, thioallcyl groups carboxylic acid derivatives, or sulfonic acid derivatives; the linking group represented by -(CII2)n-O- may be attached either through nitrogen atom or through carbon atom where n is an integer ranging from 1 - 4; Ar rep'reserits an optionally substituted divalent single or fused aromatic or heterocyclic group; R4 represents hydrogen atom, hydroxy, alkoxy, halogen, lower alkyl, optionally substituted aralkyl group or forms a bond together with the adjacent group R5;
RS represents hydrogen, hydroxy, alkoxy, halogen, lower alkyl group, acyl, optionally substituted aralkyl or RS forms a bond together with R4; R6 may be hydrogen, optionally substituted groups selected from alkyl, cycloalkyl, aryl, aralkyl, alkoxyalkyl, alkoxycarbonyl, aryloxycarbonyl, alkylaminocarbonyl, arylaminocarbonyl, acyl, heterocyclyl, heteroaryl, heteroaralkyl groups, with a provision that R6 does not represent hydrogen when R' represents hydrogen or lower alkyl group; R' may be hydrogen or optionally substituted groups selected from. alkyl, cycloalkyl, aryl, aralkyl, heterocyclyl, heteroaryl, heteroaralkyl groups; Y represents oxygen or NRB, where R8 represents 2'0 hydrogen, allcyl, aryl, hydroxyallcyl, arallcyl, heterocyclyl, heteroaryl, heteroaralkyl groups; R7 and R$ together may form a substituted or unsubstituted 5 or 6 membered cyclic structure containing carbon atoms, which may optionally contain one or more heteroatoms selected from oxygen, sulfur or nitrogen. We have also described the processes for preparing the compounds of formula (II).
The pharmaceutically acceptable salts of the general formula (I) have significant formulation and bulk handling advantages in view of the their stability.

Objective of the Invention The present invention provides pharmaceutically acceptable salts of (3-aryl-a-oxysubstituted alkylcarboxylic acids of the formula (I), their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable solvates and pharmaceutical compositions containing them or their mixtures having good stability and solubility, which can be used for the treatment and ! or prophylaxis of diseases related to increased levels of lipids, especially to treat hyperlipidemia, and for the treatment of type II diabetes, impaired glucose intolerance, leptin resistance, atherosclerosis, disorders related to Syndrome X such as hypertension, obesity, insulin resistance, coronary artery disease and other cardiovascular disorders, renal diseases including glomerulonephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis, nephropathy; retinopathy, disorders related to endothelial cell activation, psoriasis, polycystic ovarian syndrome (PCOS), dementia, diabetic complications, eating disorders, osteoporosis, inflammatory bowel diseases, myotonic dystrophy, pancreatitis, retinopathy, arteriosclerosis; xanthoma or cancer with better efficacy, potency and lower toxicity.
The present invention provides pharmaceutically acceptable salts of (3-aryl-a-oxysubstituted alkylcarboxylic acids of the formula (I) and their derivatives, their analogs, their tautomeric forms, their stereoisomers, their o polymorphs, their pharmaceutically acceptable solvates and pharmaceutical compositions containing them or their mixtures which may have agonist activity against PPARoc and / or PPARy, and optionally inhibit HMG CoA
reductase, in addition to agonist activity against PPARa and / or PPAR~y.
The present invention provides pharmaceutically acceptable salts of (3-aryl-a-oxysubstituted alkylcarboxylic acids of the formula (I) and their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable solvates and pharmaceutical compositions containing them or their mixtures having enhanced activities, without toxic effect or with reduced toxic effect.
The present invention provides a process for the preparation of pharmaceutically salts of (3-aryl-a-oxysubstituted alkylcarboxylic acids and their derivatives of the formula (I) as defined above, their analogs, their tautomeric forms, their stereoisomers, their polyrriorphs and their pharmaceutically acceptable solvates.
. The present invention provides pharmaceutical compositions containing compounds of the general formula (I), their analogs, their derivatives, their tautomers, their stereoisomers, their polymorphs, solvates or their mixtures in combination with suitable carriers, solvents, diluents and other media normally employed in preparing such compositions.
Detailed Description of the Invention The present invention relates to pharmaceutically acceptable salts having the general formula (I) O
P
1' ~° cn ,4~0 \ I ~ ORS
their derivatives, their analogs, their tautomeric forms, their' stereoisoniers, their polymorphs, wherein Rl represents hydrogen, alkyl or. aryl group; M
represents. a counter ion or a moiety which forms a pharmaceutically acceptable salt; p is an integer ranging from 1 to 2; A represents a cyclic structure given below RZ O O O
N Ni \ Ni Ni N ~ ~ N~R4 R ~ ~ N~R4 R4 N~R3 wherein R~ and R3 may be same or different and independently represent hydrogen, halogen, hydroxy, vitro, cyano, alkyl or alkoxy group; R4 represents hydrogen, ~ halogen, hydroxy, vitro, cyano, azido, formyl or unsubstituted or 5 substituted groups selected from alkyl, cycloalkyl, alkoxy, aryl, heterocyclyl, heteroaryl, amino, monoalkylamino, diallcylamino or alkoXyalkyl groups. , Suitable groups represented by Rl may be selected from hydrogen, linear or branched (Cl-C6)alkyl group, such as methyl, ethyl, ~n-propyl, 10 isopropyl, n-butyl, isobutyl, t-butyl, ~n-pentyl, isopentyl, hexyl and the like;
aryl group such as phenyl or naphthyl.
Suitable groups represented by RZ and R3 may be selected from hydrogen, halogen atom such as fluorine, chlorine, bromine 'or iodide;
hydroxy, vitro, cyano, linear or branched (CI-C6)alkyl group, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, hexyl, heptyl and the lilce; linear or branched (C~-C6)alkoxy group, such as methoxy, ethoxy, n-propoxy, isopropoxy and the like.
Suitable groups represented by R4 may be selected from hydrogen, halogen, hydroxy, vitro, cyano, azido= formyl or unsubstituted or substituted;
linear or branched (C~-C6)alkyl group, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, hexyl and the like;
unsubstituted or substituted, linear or branched (C1-C6)alkoxy group, such as rnethoxy, ethoxy, n-propoxy, isopropoxy and the like; cyclo(C3-C6)alkyl group such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl~ and the like, the cycloalkyl group may be substituted; aryl group such as phenyl or naphthyl, the aryl group may be substituted; heteroaryl group such as pyridyl, thienyl, furyl, pyrrolyl, oxazolyl, thiazolyl, iinidazolyl, oxadiazolyl, tetrazolyl, benzopyranyl, benzofuranyl and the like, the heteroaryl group may be substituted; heterocyclyl groups such as aziridinyl, pyrrolidinyl, morpholinyl, piperidinyl, piperazinyl and the like, the heterocyclyl group may be substituted; amino; monoalkylamino group such ~as NHCH3, ,NHCzHs, NHC3H7, NHC6H13, and the like, which may be substituted; diallcylamino group such as N(CH3)a, NCH3(CaHs), N(C2H5)2 and the like, which may be substituted; allcoxyalkyl group such as methoxymethyl, ethoxymethyl, methoxyethyl, ethoxyethyl and the like, which may be substituted. The substituents may be selected from halogen atom such as fluorine, chlorine, bromide or iodine; alkyl group such as methyl, ethyl, isopropyl, n-propyl, n-butyl and the like.
Suitable groups represented by M may be selected from sodium, Mg, calcium, potassium, I,i, glucamine, N-methyl glucamine; N-octyl glucamine, dicyclohexylamiile, t-butyl amine, methyl benzylamine, tris(hydroxymethyl)ainino methane (tromethamine), phenyl glycinol, lysine, arginine, metformin, aminoguanidine, aminoguanidine hydrogen carbonate, imidazole,, piperazine, dimethyl piperazine, pyrrolidine, berizylamine, phenyl glycine methyl ester, phenylalanine benzyl ester or morpholine.
Particularly useful compounds according to the present invention include (~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid phenyl glycinol salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid phenyl glycinol salt;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid phenyl glycinol salt;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid methyl benzylamine salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]=2-ethoxypropanoic acid methyl benzylamine salt;

i2 (-) . 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid methyl benzylamine salt;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid dicyclohexylamine salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoXy]phenyl]-2-ethoxypropanoic acid dicyclohexylamine salt;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid dicyclohexylamine salt;
(~) , 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid lysine salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazoliii-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid lysine salt;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid lysine salt;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid tris (hydroxymethyl)amino methane salt ;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)'ethoxy]phenyl]-2-ethoxypropanoic acid tris (hydroxymethyl)amino methane salt ;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanaic acid tris (hydroxymethyl)amino methane salt ;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4=dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid N-octyl glucamine salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquiriazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid N-octyl glucamine salt;

(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoXypropanoic acid N-octyl glucaxnine salt;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid N-methyl glucamine salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid N-methyl glucamine salt;
(-) 3-[4-[2.-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid N-methyl glucamine salt;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-~-ethoxypropanoic acid amino guanidine hydrogen carbonate salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid amino guanidine hydrogen carbonate salt;
(-) 3-[4-[2=(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid amino guanidine hydrogen carbonate salt ;
(~) 3-[4-[2-(~-Ethyl-4-oxo-3,4-dihydroquiiiazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid lithium salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid lithium salt;
3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid lithium salt;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid arginine salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid arginine salt ;

(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazoliri-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid arginine salt ;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid metformin salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid metformin salt ;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid metfornZin salt ;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid imidazole salt;
(+) ~ 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid imidazole salt;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid imidazole salt;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquilzazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt ;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]=2-ethoxypropanoic acid magnesium salt ;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoXypropanoic acid magnesium salt.;
(~) 3-[4-[2-(2-Morpholinyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt ; .
(+) 3-[4-[2-(2-Morpholinyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt;

(-) 3-[4-[2-(2-Morpholinyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt;
(~) 3-[4-[2-(2-Piperidinyl-4-oxo-3,4-dihyd~oquinazolin-3-yl)ethoxy]phenyl]-5 2-ethoxypropanoic acid magnesium salt ;
(+) 3-[4-[2-(2-Piperidinyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt ;
(-) 3-[4-[2-(2-Piperidinyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt ;
(~) 3-[4-[2-(2-Azido-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt ;
(+) , 3-[4-[2-(2-Azido-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt;
(-) 3-[4-[2-(2-Azido-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt ;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid magnesium salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid magnesium salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid magnesium salt ;
(~) 3-[4-[2-(1,5-I~imethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid magnesium salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid magnesium salt ;

(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[~;3-d]pyrimidin-6-yl)eth'oxy]phenyl]-2-ethoxypropionic acid rizagnesium salt ;
(~) ~ 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid potassium salt ;
(+) 3-[4-[2-(1-Methyl=5-ethyl-7-oxo-3-propyl-6~7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid potassium salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid potassium salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4;3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid potassium salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid potassium salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3=
d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid potassium salt ;
(~) 3-[4-[2-(1-Methyl-5=ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid calcium salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid calcium salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid calcium salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropi~onic acid calcium salt ;
(+) 3-[4=[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid calcium salt ;

(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid calcium salt;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lithium salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyriinidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lithium salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lithium salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrilnidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lithium salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lithium salt ;
(-) ' 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidiri-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lithium salt ;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-lgi-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid sodium salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4;3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid sodium salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4;3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid sodium salt ;
(~) ' 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidiii-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid sodium salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid sodium salt ;

(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1~I-pyrazolo[4,3-d]pyririzidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid sodium salt ;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)athoxy]phenyl]-2-ethoxypropionic acid arginine salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oXO-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid arginine salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid arginine salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethbxy]phenyl]-2-ethoxypropionic acid arginine salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid arginine salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid arginine salt ;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidiiz-6-yI)ethoxyjphenyl]-2-ethoxypropionic acid rriethyl benzylamine salt;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-lei-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid methyl benzylamine salt;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid rilethyl benzylamiine salt;

(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid methyl benzylamine salt;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid methyl benzylamine salt; , (-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro=1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid W ethyl benzylamine salt;
(~) 3-[4-[~-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid S-(+)-phenylglyciuol salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid S-(+)-phenylglycinol salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid S-(+)-phenylglycinol salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid S-(+)-phenylglycinol salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid S-(+)-phenylglycinol salt ;
3-[4-[2-(1,5-Dimethyl-7-ono-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid S-(+)-phenylglycinol salt ;

(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidiii-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid amirioguanidine salt 5 (+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7=dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aminoguanidine salt (-) 3-[4-[2=(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)eth'oxy]phenyl]-2-ethoxypropionic acid aW inoguanidine salt 10 ;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aminoguanidine hydrogen carbonate salt ;
15 (+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aminoguanidine hydrogen carbonate salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3 d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aminoguanidiile 20 hydrogen carbonate salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,'7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aminoguanidine hydrogen carbonate salt ; ~ .
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aminoguanidine hydrogen carbonate salt ;

(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aminoguanidiile hydrogen carbonate salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4;3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aininoguanidine salt (+) ' 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aminoguanidine salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aminoguanidine salt (~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4;3-d]pyrirriidill-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid tromethamine salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid tioriiethamW a salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid tromethamine salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid tromethamine salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid tromethamine salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro=1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid tromethamine salt ;

(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid dicyclohexylamine salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3 d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid dicyclohexylamine salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypiopionic acid dicyclohexylamine salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid dicyclohexylam~ne salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3 d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid dicyclohexylamine salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid dicyclohexylamine salt ; ~ .
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-octylglucamine salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3 d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-octylglucamine salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyriniidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-octylglucamine salt ; ~ ~.

(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7=dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-octylglucamine salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-octylglucamine salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3 d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-octylglucamine salt ;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[~,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N=methylglucamine salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-inethylglucamine salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3 d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-methylglucamine salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-methylglucamine salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-niethylglucamine salt ;

(-) 3-[4-[2-(1,5-Dimethyl-7-oa~o-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl)-2-ethoxypropionic acid N-methylglucamine salt ; ' (~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyriinidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid metforrilin salt (+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4;3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid metformin salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)'ethoxy]phenyl]-2-ethoxypropionic acid metformin salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4.,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid metformin salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid metformin salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoXy]phenyl]-2-ethoxypropionic acid metformin salt ;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lysine salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1~I-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lysine salt ; ,i_ (-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxyp'ropionic acid lysine salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoXy]phenyl]-2-ethoxypropionic acid lysine salt ; .
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyriinidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lysine salt ;

(-) 3-[4-[2-(1,5-Dimethyl-7-ox~o-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lysine salt ;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-5 d]pyrimidin-6-yl)ethoxy]phenyl]-B-ethoxypropionic acid t-butylamine salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid t-butylamine salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4;3-d]pyrimidin-6=yl)ethoxy]phenyl]-2-ethoxypropionic acid t-butylamine salt ;
(~) ~ 3-[4-[2-(1,5-Dimethyl-7-ox~o-3-propyl-6,7-dihydro-lei-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid t-butylamine salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid t-butylarnine salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid t-butylamirie salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid potassium salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid potassium salt ;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid potassium salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid magnesium salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid magnesium salt ;

(-) . 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid magnesium salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid phenyl glycinol salt;
(+) ~ 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid phenyl glycinol salt;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid phenyl glycinol salt;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid sodium salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid sodium salt ;
(-) ' 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid sodium salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanQic acid t-butylamine salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrirnidin-1-yl]ethoxy]phenyl]propanoic acid t-butylamine salt ;
(-) . 2-Ethoxy-3-[4-[2-[2-ethyl=6-oxo-4-phenyl-1,6=dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid t-butylamine salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid N-methyl glucamine salt;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid N-methyl glucamine salt;

(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid N-rizethyl glucamine salt;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid L-lysine salt ;
(+) 2-EthoXy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid L-lysine salt ;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid L-lysine salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid N-octyl glucainine salt;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid N-octyl glucamine salt;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-diliydropyrimidin-1-yl]ethoXy]phenyl]propanoic acid N-octyl glucamine salt;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid tris (hydroxymethyl)amino methane salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1 yl]ethoxy]phenyl]propanoic acid tris (hydroxymethyl)amino methane salt ;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]etho~y]phenyl]propanoic acid tris (hydroxymethyl)amino methane salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid lithium salt ;
(+) .2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid lithium salt ;

(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid lithium salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl=6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid calcium salt ;
(+) 2-Ethbxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid calcium salt ;
(-) ~ 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propaiioic acid calcium salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyririzidin-1-yl]ethoxy]phenyl]propanoic acid L-arginine salt ;
(+) . 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid L-arginine salt ;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid L-arginine salt ;
(~) ~ 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid metformin salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-.1-yl]ethoxy]phenyl]propanoic acid metformin salt ;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid metformin salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid dicyclohexylamine salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid dicyclohexylamine salt ;

(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid dicyclohexylamine salt ;
(~) ' 2-Ethoxy-3-[4-[2-[2-ethyh6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid aminoguanidine salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid aminoguanidine salt ;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid aniinoguanidine salt ;
(~) ~ 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid methyl benzylamine salt;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid methyl benzylamine salt;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-c~ihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid methyl benzylamine salt;
According to another feature of the present invention, there is provided a process ~ for the preparation of pharmaceutically acceptable salts of the formula (I) which comprises, reacting compound of the formula .(III' O
(III) ~O
where all symbols are as defined earlier with a stoichiometric amount of an appropriate base in the presence of a solvent at a temperature in the range of 10 °C to the boiling point of the solvent employed fox a period in the range of 10 minutes to 30 hours.
The compound of the formula (III) used may be either optically pure form or a racemic form. The base employed in the reaction may be selected from sodium hydroxide, sodium methoxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, magnesium hydroXide, glucamine, N-methylglucamine, N-octylglucamine, dicyclohexylaniine, t-butylamine, methyl benzylamine, tris(hydroxymethyl)aminomethane, phenyl glycinol, 5 lysine, arginine, metformin, aminoguanidine, aminoguanidine hydrogen carbonate, imidazole, piperaziiie, dimethyl piperazirie, pyrrolidine, benzylamine, phenyl glycine methyl ester, phenylalanine benzyl ester or morpholine. The solvent employed may be selected from alcohols such as ethanol, methanol, isopropanol, butanol and the like; lcetones such as acetone, 10 diethyl ketone, methyl ethyl ketone or their mixtures; ethers such as diethyl ether, ether, tetrahydrofuran, dioxane, dibutyl ether and the like or DMF, DMSO, xylene, toluene, ethyl acetate and the like or mixture thereof.
The pharmaceutically acceptable salts of the general formula (I) have significant formulation and bulk handling advantages in view of the their 15 physicochemical properties and their stability.
Various polymorphs of a compound of general formula (I) forming part of this invention may be prepared by crystallization of compound of formula (I) under different conditions. For example, using different solvents commonly 20 used or their mixtures for recrystallization; crystallizatioris at different temperatures; various modes of cooling, ranging from very fast to very slow cooling during crystallizations. Polymorphs may also be obtained by heating or melting the compound followed by gradual or fast cooling. The presence of polymorph's may be determined by solid probe NMR spectroscopy, IR
25 spectroscopy, differeritial scanning calorimetry, powder X-ray diffraction or such other techniques.
The stereoisomers of the compounds forming part of this invention may be prepared by using compound of formula (1) in its single enantiomeric form I in the process by resolving the mixture of stereoisomers by conventional methods. Some of the preferred methods include use of microbial resolution, resolving the diastereomeric salts formed with optically pure bases such as brucine, cinchona alkaloids and their derivatives, optically pure 2-alkyl phenethyl amine, phenyl glycinol and the like. The diastereomeric salts may be obtained in pure form by fractional crystallization. Commonly used methods are compiled by Jaques et al in "Enantiorriers, Racemates and Resolution" (Wiley Interscience, 1981).
Pharmaceutically acceptable solvates of the compounds of formula (I) forming part of this invention may be prepared by conventional methods such as dissolving the compounds of formula (I) in solvents such as water, methanol, ethanol and the like, preferably water and recrystallizing by using different crystallization techniques.
The present invention provides a pharmaceutical composition, containing the compounds of the general formula (I) as defined above, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable solvates in combination with the usual pharmaceutically employed carriers, diluents and the like, useful for the treatment and / or prophylaxis of diseases such as hypertension, coronary heart disease, atherosclerosis, stroke, peripheral vascular diseases and related disorders. These compounds are useful for the treatment of familial hypercholesterolemia, hypertriglyceridemia, lowering . of atherogenic lipoproteins, VLDL and LDL. The compounds of the present invention can be used for the treatment of certain renal diseases including glomerulonephri'tis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis, nephropathy. The compounds of general formula (I) are also useful for the treatrizent/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, as inflammatory agents, treating diabetic complications, disorders related to endothelial cell activation, psoriasis, polycystic ovarian syndrome (PCO.S), inflammatory bowel diseases, osteoporosis, myotonic dystrophy, pancreatitis, retinopathy, arteriosclerosis, xanthoma and for the treatment of cancer. The compounds of the present invention are useful in the treatment and/or prophylaxis of the above said diseases in combination/concomittant with one or more HMG CoA reductase inhibitors, hypolipidemic/ hypolipoproteinemic agents such as fabric acid derivatives, nicotinic acid, cholestyramine, colestipol, probucol or their combination. The compounds of the present invention ' in combination with HMG CoA reductase inhibitors, hypolipidemic/hypolipoproteinemic agents can be administered together or within such a period to act synergistically. The IzTi~IG CoA reductase inhibitors nlay 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 fabric acid derivative may be gemfibrozil, ~ clofibrate, fenofibrate, ciprofibrate, benzafibrate and their analogs thereof.
The present invention also provides a pharmaceutical composition, containing the compounds of the general formula (I) as defined above, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable solvates and one or more HMG
CoA reductase inhibitors, hypolipidemic a hypolipoproteineinic agents such.as fabric acid derivatives, nicotinic acid, cholestyramine, colestipol, probucol ~ in combination with the usual pharmaceutically employed carriers, diluents and the like.
The pharmaceutical composition may be in the forms normally employed, such as tablets, capsules, powders, syrups, solutions, suspensions and the like, may contain flavorants, sweeteners etc. in suitable solid or liquid carriers or. diluents, or in suitable sterile media to form injectable solutions or suspensions. Such compositions typically contain from 1 to 20 %, preferably 1 to 10 % by weight of active compound, the remainder of the composition being pharmaceutically acceptable carriers, diluents or solvents.
Suitable pharmaceutically acceptable carriers include solid fillers or diluents and sterile aqueous or organic solutions. The active ingredient 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 active ingredient can be combined with a suitable solid or liquid carrier or diluent to form capsules, tablets, powders, syrups, solutions, suspensions and the like. The pharmaceutical compositions, may, if desired, contain additional components such as flavourants, sweeteners, excipients and the like. For parenteral administration, the active ingredient can be combined with sterile aqueous or organic media to form injectable solutions ~or 1 S 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. Aqueous solutions with the active ingredient dissolved in p~olyhydroxylated castor oil may also be used for injectable solutions. The injectable solutions prepared in this manner can then be administered intravenously, intraperitoneally, subcutaneously, or intramuscularly, with intramuscular administration being preferred in humans.
For nasal administration, the preparation may contain the active ingredient of the present invention dissolved or suspended in a liquid carrier, in particular an aqueous carrier, for aerosol application. The carrier may contain additives such as solubilizing agents, such as propylene glycol, surfactants, absorption enhancers such as lecithin (phosphatidylcholine) or cyclodextrin or preservatives such as parabenes.

Tablets, dragees or capsules having talc and / or a carbohydrate carried binder arid the like are particularly suitable for any oral application.
Preferably, carriers for tablets, dragees or capsules include lactose, corn starch and / or potato starch. A syrup or elixir can be used in cases where a sweetened vehicle can be employed.
A typical tablet production method is exemplified below °.
')<'alilet Production Example a) 1) Active ingredient 30 g 2) Lactose 95 g 3) Corn starch 30 g 4) Carboxymethyl cellulose 44 g 5) MagnesiLUn stearate 1 g 200 g for 1000 tablets The ingredients 1 to 3 are uniformly blended with water and granulated after drying under reduced pressure. The ingredient 4 and 5 are' mixed well with the granules and compressed by a tabletting machine to prepare 100'0 tablets each containing 30 mg of active ingredient:
b) 1) Active ingredient30 g 2) Calcium phosphate 90 g 3) Lactose 40 g 4) Corn starch 35 g 5) Polyvinyl pyrrolidone 3.5 g 6) Magnesium stearate 1.5 g 200 g for 1000 tablets The ingredients 1-4 are uniformly moistened with an aqueous solution of 5 and granulated after cliying under reduced pressure. Ingredient 6 is added and granules are compressed by a tabletting machine to prepare 1000 tablets containing 30 mg of ingredient 1.
The compound of the formula (I) as defined above are clinically 5 administered to mammals, including man, via either oral, nasal, pulmonary, transdermal or parenteral, rectal, depot, subcutaneous, intravenous, intrauxethral, intramuscular, intranasal, ophthalmic solution or an ointment.
Administration by the oral route is preferred, being more convenient and avoiding the possible pain and irritation of injection. However, ili 10 circumstances where the patient cannot swallow the medication, or absorption following oral administration is impaired, as by disease or other abnormality, it is essential that the drug be administered parenterally. By eider route, the dosage is in the range of about 0.01 to about 100 ing / kg body weight of the subject per day or preferably about O.Ol to about 30 mg / kg body weight per 15 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.
20 The invention is explained in detail in the examples given below which are provided by way of illustration only and therefore should not be construed to limit the scope of the invention.
(-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-25 , ethoxypropanoic acid was prepared according to the procedure given in WO
9910g501 as given below A solution of [(2S)-N(1S)]-2-ethoxy-3-[4-[2-(2,-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid-N-(2-g 3) Lactose hydroxy-1-phenylethyl)propanamide (267 mg, 0.504 mmol) in a mixture of 11VT sulphuric acid and dioxane ! water was heated at 100 °C for 16 h.
The reaction mixture was cooled to ca 25 °C and dioxane was removed under reduced pressure. The remaining solution was cooled in an ice bath and the white solid precipitated was filtered and dried to afford (-)-3-[4-[2-(2-ethyl-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid (170 mg, 82 %).
However, any other procedure for preparing (-)-3-[4-[2-(2-Ethyl-4-oxo 3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid can be used. (~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]
2-ethoxypropanoic acid , and (+)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid can be prepared by a similar procedure described above.
Example-1 (-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2,-ethoxypropanoic acid phenyl glycinol salt O _ Ph . I w NCO ~ /. ~ ~ . ~ OH
C-O NH
Et0 (-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid (2 g) and isopropanol (50 ml) was added to 250 ml four necked round bottom flask fitted with a mechanical stirrer and reflux condenser: The reaction mixture was slowly heated to 45-55 °C for complete dissolution of the. reaction mass. Phenyl glycinol (0.667 g) dissolved in isopropanol (10 ml) was added to the reaction mixture at 45-55 °C in about 10 min. under stirring. The progress of the reaction was maintained by gentle reflux of reaction mixture at 75-85 °C for 10 h. The reaction mixture was cooled to room temperature and stirred for 5 h at room temperature. The precipitated product was filtered, dried at 60 °C for 2-3 h to afford pure phenyl glycinol salt of (-)-3-[4-[2-(2-ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid as free flowing white crystalline solid, (weighs about 2 g, yield 75 %, mp : 105 -107 °C, purity 99 % by HPLC).
IR (KBr) ciri 1 : 3400-3300 (O-H stretch), 2922 (-C-H aliphatic stretch), 1670 (-COO- stretch), 1590(-CONH stretch), 1420 (-COO stretch).
1H NMR (200 MHz, DMSO-d6) 8 : 8.13 (d, J=7.89Hz, 1H), 7.82 (t, J=7.01Hz, 1H), 7.64 (d, J=8.21Hz, 1H), 7.50 (t, J= 7.26Hz, 2H), 7.4 (s, SH), 7.13 (d, J=
8.SOHz, 2H), 6.84 (d, J=B.SOHz, 2H),'4.47 (t, J=5.19Hz, 2H), 4.4 (d, 2H), 4.26 (t, J=5,19Hz, 2H), 3.99-3.84 (m, 1H), 3.60-3.40 (m, 1H), 3.40-3.20 (m, 2H), 3.06 (q, J= 6.96Hz, 2H), 2.88 (q, J= 6.64Hz, 2H), 1.32.(t, J= 7.17Hz, 3H), 1.02 (t, J= 6.96Hz, 3H).
Mass m/z .: 411 (M+ + 1), 137 (C$H11N0). Anal. Calcd : C31H37N3O6; % C
68.00; % H 6.76; % N 7.67, Found % C 67.80; % H 6.56; % N 7.57.
Example-2 (-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid R-(+) methyl benzylamine salt .

O
~ HBO ~ ~ , C_O~ , I W CH3 Et~
(-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoXy]phenyl]-2-ethoxypropanoic acid (2.0 g) and isopropanol (50 m1) was added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 45-55 °C for complete dissolution of the reaction mass. R-(+) methyl benzylamine (0.589 g) in isopropanol (10 m1) was added to the reaction mixture at 45-55 °C in about 10 min. under stirring. The progress of the reaction was maintained by gentle reflux of reaction mixture at 75-85 °C for 10 h. The reaction mixture was cooled to room temperature and stirred for 12 h at room temperature. The reaction mixture was cooled to -5 °C and maintained at that temperature for 2 h under stirring. The precipitated product was filtered, dried at 60 °C
for 2 h to afford pure (R)-(+)-methyl benzylamine salt of (-)-3-[4-[2-(2-ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid as free flowing off white amorphous solid, (weighs about 2 g, yield 80 %, mp : 137-139 °C, purity 99 % by HPLC).
IR (KBr) crri 1 : 3400-3300 (N-H stretch), 3120 (-C-H aromatic), 2930 (-C-H
aliphatic), 1660 (-COO stretch), 1583 ,(-CONH stretch), 1400 (=COO stretch).
1H NMR (200 MHz; DMSO-d6) b : 8.13 (d; J=7.89Hz, 1H), 7.82. (t; J=7.OlHz, 1H), 7.64 (d, J=8.21Hz, 1H), 7.6-7.2 (m, SH), 7.50 (t, ~= 7.26Hz, 2H), 7.13 (d, J= B.SOHz, 2H), 6.84 (d, J=8.SOHz, 2H), 4.47 (t, J=5.19Hz, 2H), 4.26 (t, J=5.19Hz, 2H), 3.99-3.84 (m, 1H), 3.60-3.40 (m, 1H); 3.40-3:20 (m, 1H), 3.06 (q, J= 6.96Hz, 2H), 2.88 (q, J= 6.64Hz, 2H), 1.32 (t, J= 7.17Hz, 3H), 1.02 (t, J= 6.96Hz, 3H), 1.0 (d, 3H).
Mass mlz : 411 (M+ + 1), 121 (C8H11N). Anal. Calcd. C31H37N3O5, %. C
70.05, % H 6.96; % N 7.90%; Found % C 69.82; % H 6.80; % N 7.70.
Example-3 (-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid dicyclohexylamine salt .

H
. <
Et0 (-)-3-[4-[2-(2-Ethyl-4-oxo-3,4~dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid (2 g) and isopropanol (50 ml) was added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 45-55 °C for complete dissolution of the mass. Dicyclohexylamine (0.88 g) dissolved in isopropanol (10 ml) was added to the reaction mixture at 45-55 °C in about 10 Thin.
under stirring. The progress of the reaction was maintained by gentle reflux of reaction mixture at 75-85 °C for 10 h. The reaction mixture was cooled to 0-5 °C and maintained for 2 h under stirring. The precipitated product was filtered, dried at 60 °C fox 2-3 h to afford pure dicyclohexylamine salt of (-)-3-[4-[2-(2-ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid as free flowing off white crystalline solid, (weighs about 2.2 g, yield % mp : 152-153 °C; purity 99 % by HPLC).
IR (I~Br) cm 1 : 3400-3300 (-N-H stretch), 3100 (C-H, aromatic), 2930 (=C-H, aliphatic), 1670 (-COO stretch), 1597 °(-CONH stretch), 1400 (-COO
stretch).
1H NMR (200 MHz, DM80-d6) b : 8.13 (d, 3=7.89Hz, 1H), 7.82 (t, J=7.OlHz, 1H), 7.64 (d, J=8.21Hz, 1H), 7.50 (t, J= 7.26Hz, 2H), 7.13 (d, J= 8.SOHz, 2H), 6.84 (d, J=8.SOHz, 2H), 4.47 (t, J=5.19Hz, 2H), 4.26 (t, J=5.19Hz, 2H), 3.99-3.84 (m, 1H), 3.60-3.40 (m, 1H), 3.40-3.20 (m, 1H), 3.06 (q, J= 6.96Hz, 2H), 2.88 (q, J= 6.64Hz, 2H), 2.6-0.8 (m, 22H), 1.32 (t, J= 7.17Hz, 3H), 1.02 (t, J=
6.96Hz~ 3H).
Mass mlz : 411 (M+ + 1), 181 (Cl2HasN). Anal. Calcd :°C35H49N3O5;
% C
71.06;%H8.29;%N7.10;Found°/~C70.89;%H8.10;%N6.95.
Example 4 .
(-)-3-[4-[Z-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl-2-ethoxypropanoic acid lysine salt O
O NHs NCO \ / O~0 . (CH2)4 H-,-NH2 Et0 COOH
(-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid (2 g) and isopropanol (50 ml) was added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 45-55 °C for complete dissolution of the mass. Lysine (0.8 g) dissolved in isopropanol (10 ml) was added to the reaction mixture at 45-55 °C in about 10 min. under stirring. The 5 progress of the reaction was maintained by the gentle reflux of reaction mixture at 75-85 °C for 10 h. The reaction mixture was cooled to room temperature and stirred for 12 h at room temperature. The precipitated product was filtered, dried at 60 °C for 2-3 h to afford pure lysine salt of (-)-3-[4-[2-(2-ethyl-4-oxo-3,4-dihydroquinazolin=3-yl)ethoxy]phenyl]-2-ethoxypropanoic 10 acid as free flowing off white amorphous solid (weights about 2 g, yield :

%, mp : 152-155 °C purity 99 % by HPLC).
IlZ (KBr) cm 1 : 3400-3300 (N-H stretch), 3120 (-C-H, aromatic), 2930 (-C-H
aliphatic), 1670 (-COO stretch), 1584 (-CONH stretch), 1407 (-COO stretch).
1H NMR (200 MHz, DMSO-d6) 8 : 8.13 (d, J=7.89Hz, 1H), 7.82 (t, J=7.01Hz, 15 1H), 7.64 (d, J=8.21Hz, 1H), 7.50 (t, J= 7.26Hz, 2H), 7.13 (d, J= 8.50Hz, 2H), 6.84 (d, J=8.50Hz, 2H), 4.47 (t, J=5.19Hz, 2H), 4.26 (t, J=5.19Hz, 2H), 3.99-3.84 (m, 1H), 3.60-3.40 (m, 1H), 3.40-3.20 (m, 1H), 3.19 (t, 2H), 3.06 (q, J=
6.96Hz, 2H), 2.88 (q, J= 6.64Hz, 2H), 2.63 (t, 2H), 1.52 (m, 2H), 1.32 (t, J=

7.17Hz, 3H), 1.32 (m, 2H), 1.02 (t, J= 6.96Hz, 3H).
20 Mass m!z : 411 (M+ + 1), 146 (C6H14NZO2). Anal. Calcd : C~9H4pN4O7 ; % C
62.5; % H 7.19; % N 10.07; Found % 062.35; % H 7.10; % N 9.89.
Example 5 (-)-3-[4-[2-(2-Ethyl=4-oxo-3,4=dihydroquinazolin-3-yl)ethoxy] phenyl]-2-25 ethoxypropanoic acid tris (hyd~oxymethyl)amino methane salt O
HO OH
NCO ~ / O O . ~
C-O 0.,. Hs~OH
N~ Et0 (-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoXypropanoic acid (2 g) and isopropanol (50 rizl) was added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and xeflux condenser. The reaction mixture was slowly heated to 45-55 °C for complete dissolution of the mass. Tris (hydroxymethyl) amino methane (0.59 g) dissolved in isopropanol (10 ml) was added to the reaction mixture at 45-55 °C in about 10 min. under stirring. The progress of the reaction was maintained by gentle reflux of reaction mixture at 75-85 °C for 10 h.
The reaction mixture was cooled to room temperature and stirred for 12 h. Distill off the isopropanol on rotavapor bath at 45-55 °C under vacuum. The product could i~ot be isolated as a fine solid, because of hygroscopic nature and obtained as a sticky gummy mass, (weighs about 2 g, yield 77 %, purity 99 by HPLC).
IR (I~Br) cm ~ : 3400-3300 (N-H stretch), 3100 (C-H aromatic), 2937 (-C-H
aliphatic), 1670 (-COO stretch), 1584 (-CONH stretch), 1395 (-COO stretch).
1H NMR (200 MHz, DMSO-d6) 8 : 8.13 (d, J=7.89Hz, 1H), 7.82 (t, J=7.01Hz, 1H), 7.64 (d, J=8.21Hz, 1H), 7.50 (t, J= 7.26I3z, 2H), 7.13 (d, J= 8.SOHz, 2H), 6.84 (d, J=8.SOHz, 2H), 4.47 (t, J=5.19Hz, 2H), 4.26 (t, J=5.19Hz, 2H), 3.99-3.84 (m, 1H), 3.8 (s, 6H), 3.60-3.40 (m, 1H), 3.40-3.20 (iii, 1H), 3.06 (q, J=
6.96Hz, 2H), 2.88 (q, J= 6.64Hz, 2H), 1.32 (t, J= 7.17Hz, 3H), 1.02 (t, J=
6.96Hz, 3H).
Mass. mlz : 411 (M+ + 1), 121 (C4H11N03).
Example 6 (-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid N-octyl glucamine salt CH2-NH2-C$H~~
O H OH
W NCO ~ ~ O_O . WO H
Et0 H OH
N H' OH

(-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid (2 g) and isopropanol (50 ml) was added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 45-55 °C for complete dissolution of the mass. N-octyl glucarriine salt (1.42 g) dissolved ~in isopropanol (10 ml) was added to the reaction mixture at 45-55 °C in about 10 min. under stirring. The progress of the reaction was maintained by the gentle reflux of reaction mixture at 75-85 , °C for 6 h. The reaction mixture was cooled to room temperature and stirred for 12 h. The precipitated product was filtered and dried at 60 °C for 2-3 h to afford pure N-octyl glucamine salt (-)-3-[4-[2-(2-ethyl-4=oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxy propanoic acid as free flowing off white crystalline solid, (weighs about 2.7 g, yield 92 %, Trip : 114-116 °C, purity 99 % by HPLC).
IR (I~Br) cm 1 : 3400-3250 (-N-H stretch), 2926 (-C-H stretch), 2800-2200 (-NH3 stretch), 1776 (-COO stretch), 1593 (-CONH stretch), 1410 (-COO
stretch).
1H NMR (200 MHz, DMSO-d6) 8 : 8.13 (d, J=7.89Hz; 1H), 7.82 (t, J=7.OlHz, 1H),'7.64 (d, J=8.21Hz, 1H), 7.50 (t, ~= 7.26Hz, 2H), 7.13 (d, J= 8.50Hz, 2H), 6.84 (d, J=8.50Hz, 2H), 4.47 (t, J=5.19Hz, 2H), 4.26 (t, J=5.19Hz, 2H), 4.2-3.06 (m, 8H), 3.99-3.84 (m, 1H), 3.60-3.40 (m, 1H), 3.40-3.20 (m, 1H), 3.06 (q, J= 6.96Hz, 2H), 2.88 (q, J= 6.64Hz, 2H), 1.5 (d, 3H), 1.40-1.00 (m, 1~6H), 1.32 (t, J= 7.17Hz, 3H), 1.02 (t, J= 6.96Hz, 3H).
Mass m/z ~: 411 (M+ +1), 293 (C14H3iNOs). Anal. Calcd. C37,H57N3O1o, % C
63.15; % H 8.10; % N 5.97; Found %C 63.01; %H 7.91; %N 5.73.

Example 7 (-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid N-methyl glucamine salt O

O H OH
\ NCO ~ ~ 0_0 . HO H
~ ~~ Et0 H OH
H OH

(-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxyproparloic acid (2 g) and isopropanol (50 ml) was added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 45-55 °C for complete dissolution of the mass. N-methyl glucamine (0.95 g) in isopropanol (20 ml) was added to the reaction mixture at 45-55 °C in about 10 min. under stirring.
The progress of the reaction was maintained by gentle reflux of reaction mixture at 75-85 °C for 5 h. The reaction mixture was cooled to RT and stirred for 12 h at room temperature. The precipitated product was filtered, and dried at 60 °C for 2-3 h to afford pure N-methyl glucarriine salt of (-)-3-[4-[2-(2-ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid as free flowing off white crystalline solid, (weighs about 2.75 g, yield : 93 %, mp : 114-116 °C, purity 99 % by HPLC).
IR (KBr) cm 1 : 3350-3300 (-NH, -OH stretching), 2960 (C-H stretch), 1670 (-COO stretch), 1887 (-CONH stretch).' 1H NMR (200 MHz, DMSO-d6) 8 : 8.13 (d, J=7.89Hz, 1H), 7.82 (t, J=7.01Hz, 1H), 7.64 (d, J=8.21Hz, 1H), 7.50 (t, J= 7.26Hz, 2H), 7.13 (d, J= 8.SOHz, 2H), 6.84 (d, J=8.SOHz, 2H), 4.47 (t, J=5.19Hz, 2H), 4.26 (t, J=5.19Hz, 2H), 4.0-3.26 (m, $H), 3.99-3.84 (m, 1H), 3.60-3.40 (m, 1H), 3.40-3.20 (m, 1H), 3.06 (q, J= 6.96Hz, 2H), 2.88 (q, J= 6.64Hz, 2H), 2.4 (s, 3H), 1.32 (t, J= 7.17Hz, 3H), 1.02 (t, J= 6.96Hz~ 3H).
Mass m/z : 411 (M+ + 1), 195 (C7H17N0=). Anal. Cacld. C3oH43N3~10~ % C
59.5;%H7.10;%N6.94;Found%C59.25;%H6.9;%N6.74.
Example 8 (-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)etho~y]phenyl]-2-ethoxypropanoic acid aminoguanidine hydrogen carbonate salt O O ~ NIIH
\ ~ ~ ~ C~O~ . H3N.N~ 0. HCOO
Et0 H
(-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoXy]phenyl]-2-ethoxypropanoic acid (2 g) and isopropanol (50 ml) was added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 45-55 °C for complete dissolution of the mass. Aminoguanidine hydrogen carbonate (0.662 g) ll1 isopropanol (20 ml) was added to the reaction mixture at 45-55 °C in about 10 min. under stirring. The progress of the reaction was maintained by gentle reflux of reaction mixture at 75-85 °C for 10 h. The reaction rilixture was cooled to room temperature and stirred for 12 h at room terilperature. Distill off the isopropanol on rotavapor water bath at 45-55 °C under stirring.
The product could not be isolated as fme solid, because of hyg~oscopic nature and obtained as sticky gummy mass (weighs about 2 g, yield 75 %, purity 99 % by HPLC).
IR (KBr) cm 1 : 3400-3300 (N-H~ stretch), 2970 (=C-H, aliphatic stretch), 1675 (-COO stretch), 1595 (-CONH stretch), 1392 (-COO stretch).
1H NMR (200 MHz, DMSO-d6) 8 : 8.13 (d, J=7.89Hz, 1H), 7.82 (t, J=7.Olliz, 1H), 7.64 (d, J=8.21Hz, 1H), 7.50 (t, J= 7.26Hz, 2H), 7.13 (d, J= 8.50Hz, 2H), 6.84 (d, J=8.50Hz, 2I3), 4.47 (t, J=5.19Hz, 2H), 4.26 (t, J=5.19Hz, 2H), 3.99-3.84 (m, 1H), 3.60-3.40 (m, 1H), 3.40-3.20 (m, lI~), 3.06 (q, J= 6.96Hz, 2H), 2.88 (q, J= 6.64Hz, 2H), 2.4 (s, 6H), 1.32 (t, J= 7.17Hz, 3H), 1.02 (t, J=
6.96Hz, 3H).
Mass m/z : 411 (M~ +1), 136 (CZH8N402).

Exaanple 9 (-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid lithium salt o _ O ~ ~ O-po . Lid Et0 10 (-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid (5 g) and isopropanol (100 ml) was added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was, slowly heated to 45-55 °C for complete dissolution of the mass. Lithium hydroxide hydrate (0.51 g) dissolved in water 15 (20 ml) was added to the reaction mixture and heated to 75-85 °C for 12 h and monitor the progress of the reaction. The reaction mixture was cooled to room temperature and stirred for 12 h at room temperature. Distill off the isopropanol on rotavapor water bath at 45-55 °C under vacuum.
Isopropanol (50 ml) was added and the precipitated product was filtered, dried at 60 °C for 20 2-3 to afford pure lithium salt of (-)-3-[4-[2-(2-ethyl-4-oxo-3;4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid as off white crystalline solid, (weighs about 4.5 g, yield : 90 %, mp, : 245-47 °C, purity 99 by HPLC). .
IR (KBr) cm 1 : 3120 (-C-H aromatic), 2930 (-C-H aliphatic), 1660 (-COO
25 stretch), 1587 (-CONH stretch), 1400 (-COO stretch).
1H NMR (200 MHz, DMSO-d6) 8 : 8.13 (d, J=7.89Hz, 1H), 7.82 (t, J=7.OlHz, 1H), 7.64 (d, J=8:21Hz, 1H), 7.50 (t, J= 7.26Hz, 2H), 7.13 (d, J= 8.50Hz, 2H), 6.84 (d, J=B.SOHz, 2H), 4.47 (t, J=5.19Hz, 2H), 4.26 (t; J=5.19Hz, 2H), 3.99-3.84 (m, 1H), 3.60-3.40 (m, 1H), 3.40-3.20 (m, 1H), 3.06 (q, J= 6:96Hz, 2H), 2.8~ (q, J= 6.64Hz, 2H); 1.32 (t, J= 7.17Hz, 3H), 1.02 (t, J= 6.96Hz, 3H).
Mass m/z : 411 (M+ + 1). Anal. Calcd : C23H25N205Li; % C 66.34; % H 6.00;
% N .6.73; Found % C 66.12; % H 5.99; % N 6.53.
Example 10 (-)-3-[4-[2-(B-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt O
~ N~o Et0 (-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid (6 g) and isopropyl alcohol (60 ml) was added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 45-55 °C for complete dissolution of the mass. Magnesium hydroxide (0.423 g) was added to the reaction mixture and heated to 75-85 °C for 12 h and monitored the progress of the reaction. The reaction mixture was cooled to RT and stirred for 12 h at room temperature. Distill off the isopropanol on rotavapor water bath at 45-55 °C under vacuum and added isopropanol (5 ml) to the glassy residue and stirred for 10 min. The precipitated product was filtered, dried at 60 °C for 2-3 h to afford pure magnesium salt of (-)-3-[4-[2-(2-ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid as free flowing off white amorphous solid, (weighs about 5 g, yield : 80 %, nip : >25U
°C, purity 99% by HPLC).
IR (KDr) cm 1 : 3120 (-C-H aromatic), 2930 (-C-H aliphatic), 1660 (-COO
stretch), 1587 (-CONH stretch), 1400 (-COO stretch).

1H NMR (200 MHz, DMSO-d6) 8 : 8.13 (d, J=7.89Hz, 1H), 7.82 (t, J=7.OlHz, 1H), 7.64 (d, J=8.21Hz, 1H), 7.50 (t, J= 7.26Hz, 2H), 7.13 (d, J= 8.SOHz, 2~I), 6.84 (d, J=8.SOHz, ZH), 4.47 (t, J=5.19Hz, 2H), 4.26 (t, J=5.19Hz, 2H), 3.99 3.84 (m, 1H), 3.60-3.40 (m, 1H), 3.40 -3.20 (m, 1H), 3.06 (q, J= 6.96Hz, 2H), 2.88 (q, J= 6.64Hz, 2H), 1.32 (t, J= 7.17Hz, 3H), 1.02 (t, J= 6.96Hz, 3H).
Mass m/z : 411 (M+ + 1). Anal. Calcd : C46HSON4010Mg~ % C 65.63; % H
5.94; % N 6.65; Found % C 65.50; % H 5.75; % N 6.50.
Example 11 Form ~
(-)-3-[4-(B-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy] phenyl]-2-ethoxypropanoic acid arginine salt W NCO ~ / IOCI-OO , HN~N~C02H
Et0 ~ NH3 (-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2 ethoxy propanoic acid (4.1 g), isopropanol (50 ml) was added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 45-55 °C in about min. under stirring. L-Arginine (1.74 g) was dissolved in DM water (5 ml) and added' at 45-55 °C under stirring. Maintained the gentle reflux of reaction mixture at 75-85 °C for 10 h and monitored the progress of the reaction. The reaction mixture was cooled to room temperature and stirred for 12 h at room temperature. Distill off the isopropanol on rotavapor bath at 45-55 °C
under . vacuum and added isopropanol (5 ml) to the glassy residue and stirred for 10 min. . The precipitated product was filtered, , dried at 60 °C for 2-3 h to afford form I of pure arginine salt of ~ (-)-3-[4-[2-(2-ethyl=4-oxo-3,4 dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxy propanoic acid as off white amorphous solid (weights about 4.67 g, yield : 80%, W ~p : 215 °C, purity 99 by HPLC).
IR (KBr) cm 1 : 34f0-3300 (N-H stretch), 3120 (-C-H, aromatic), 2930 (-C-H
aliphatic), 1670 (-COO stretch(, 1584 (-CONH stretch), 1407 (-COO stretch).
1H NMR (200 MHz, DMSO-d6) b : 8.13 (d, J=7.89Hz, 1H), 7.82 (t, J=7.OlHz, 1H), .7.64 (d, J=8.21Hz; 1H), 7.50 (t, J= 7.26Hz, 2H), 7.13 (d; J= 8.50Hz, 2H), 6.84 (d, J=8.SOHz, 2H), 4.47 (t, J=5.19Hz, 2H), 4.26 (t, J=5.19Iiz, 2H), 3.99-3 . 84 (m, 1 H), 3. 8-3 .2 (m, 7H); 3 .60-3 .40 (m, 1 H), 3 .40-3 .20 (m, 1 H), 3.19 (t, 2H), 3.06 (q, J= 6.96Hz, 2H), 2.88 (q, J= 6.64Hz, 2H), 2.63 (t, 2H), 1.52 (m, 2H), 1.32 (t, J= 7.17Hz, 3H), 1.32 (m, 2H), 1.02 (t, J= 6.96Hz, 3H).
Mass m/z : 411 (M+ + 1). Anal. Calcd : C29H4oN607 ; .% C 59.57; % H 6.84;
N 14.38; Found % C 59.40; % H 6.00; % N 13.28.
Form a (-)-2-Ethoxy-3-[4-[2-(2-ethyl-4-oxo-3,4-dihydro-3-quinazolinyl)ethoxy]
phenyl]propionic acid ( 140 g), isopropanol (2.8 L) was added to 5 L four necked round bottom flask, fitted ' with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 65-75 °C in about min. under stirring. L-Arginine (59.2 g) dissolved in demineralized (DM) water (296 ml) was added at 65-75 °C under stirring. After addition of the arginine solution, the reaction mixture becomes clear and precipitation appeared immediately in the reaction mixture. Maintained the gentle reflux of reaction mixture at 75-85 °C for 4-8 h and monitored the progress of the reaction. The reaction mixture was cooled to room temperature and stirred for 2 h at room temperature. The precipitated product was filtered, dried at 60-65 °C for 5-6 h, till moisture content (MC) reached <1 %, to afford form II of pure arginiiie salt of (-)-3-[4-[2-(2-ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid as white crystalline solid, (weights about 1.80 g; yield : 90 %, Trip 216-220 °C, purity 99 % by HPLC).

IR (I~Br) cm 1 : 3400-3300 (N-H stretch), 312,0 (-C-H, aromatic), 2930 (-C-H
aliphatic), 1712 (-COOH), 1670 (-COO stretch, -CONH stretch), 1584 (-CONH stretch), 1407 (-COO stretch).
1H NMR (200 MHz, DMSO-d6) 8 : 8.13 (d, J=7.89Hz, 1H), 7.82 (t, J=7.OlHz, 1H), 7.64 (d, J=8.21Hz, 1H), 7.50 (t, J= 7.26Hz, 2H), 7.13 (d, J= 8.50Hz, 2H), 6.84 (d, J=8.50Hz, 2H), 4.47 (t, J=5.19Hz, 2H), 4.26 (t, J=5.19Hz~ 2H), 3.99-3.84 '(m, 1H), 3.8-3.2 (m, 7H), 3.60-3.40 (rim, 1H), 3.40-3.20 (m, 1H), 3.19 (t, 2H), 3.06 (q, J= 6.96Hz, 2H), 2.88 (q, J= 6.64Hz, 2H), 2.63 (t, 2H), 1.52 (m, 2H), 1.32 (t, J= 7.17Hz, 3H), 1.32 (m, 2H), 1.02 (t, J= 6:96Hz, 3H).
Mass mlz : 411 (M+ + 1). Anal. Calcd : Ca9H4oN607 ; % C 59.57; % H 6.84;
N 14.38; Found % C 59.40; % H 6.00; % N 13.28.
Example 12 (-)-3-[4-[2-(2-Azido-4-oXO-3,4-dihydroquinazoliri-3-yl)ethoxy]phenyl]-2- .
ethoxypropanoic acid anagnesium salt W N~0 ~ / ~-OO M O+

N~N3 Et0 (-)-3-[4-[2-(2-Azo-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid (61 mg), dry methanol (5 ml) and magnesium hydroxide (3.98 mg)~ was added to 50 ml one necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was refluxed at 80 °C for 12 h and monitored the progress of the reaction. The reaction mixture was cooled to RT and distill off the methanol. The residue was washed with dry ether and dried under vacuuriz to afford pure magnesium salt of (-)-3-[4-[2-(2-azo-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid a solid, (weighs about 61 m g, yield : 48.8 %, mp : 230 -235 °C, purity 90.75 % by HPLC).

IR (KBr) cm~l : 3425, 2926, 1696, 1624, 1565.
1H NMR (200 MHz, CDC13) 8 : 8.39 (d, J=7.89Hz, 1H), 8.29 (d, J=7.89Hz, 1H), 8.05 - 7.95 (m, 1H), 7.8-7.7 (m, 1H), 7.10 (d, J=8.21Hz, 2H), 6.74 (d, J=7. 8 9Hz, 2H), 4.4 - 4.3 (m, 4H), 3 . 8 - 3 . 7 (m, 1 H), 3 . 6 - 3 . 5 (m, 1 H), 3 .4 -5 3.2 (m, 1H), 3.0 - 2.8 (m, 1H), 2.8 - 2.7 (m, 1H), 1.06 (t, J-6:64Hz, 3H).
Example 13 (-)-3-[4-[2-(2-Morpholinyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]
phenyl]-2-ethoxypropanoic acid magnesium salt \ N~° ~ ~ ~_00 M O
~ ~~N~ Et0 10 ~0 2 (-)-3-[4-[2-(2-Morphoinyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid (160 mg), dry methanol (5 ml) and magnesium hydroxide (9.45 mg) was added to 50 ml one necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was 15 refluXed at 80 °C for 12 h and monitored the progress of the reaction. 'The reaction mixture was cooled to RT and distill off the methanol. The residue was washed with dry ether and dried under vacuum to afford pure magnesium salt of (-)-3-[4-[2-(2-morpholinyl-4-oxo-3,4-dihydroquiriazolin-3-yl)ethoxy]
phenyl]-2-ethoxypropanoic acid a solid, (weighs about 100 rim g, yield : 30.58 20 %, mp : 250 - 255 °C, purity 90.43 % by HPLC).
IR (KBr) cm 1 : 3441, 2924, 2854,1674, 1610, 1587 1H NMR (200 MHz, CDC13) S : 8.16 (d, J=7.89Hz, 1H), 7.71 (d, J=7.06Hz, 1H), 7.60 - 7.50 (m, 1H), 7.50 = 7.35 (m, 1H), 7.16 (d, J=7.98Hz, 2H), 6.75 (d, J=8.21Hz, 2H), 4.56 (t, J = 8. l4Hz, 3H), 4.40 - 4.30 (m, 3H), 3.90 -.
3.65 25 (m, 4H), 3.65 - 3.50 (m, 2H), 3.40 - x.10 (m, SH), 3.05 - 2:90 (m, 1H), 2.90 -2.70 (m, 1H), 1.15 - 1.00 (m, 3H).

Example 14 (-)-3-[4-[2-(2-Piperidinyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy] phenyl]
-B-ethoxypropanoic acid magnesium salt O
O +
\ NCO ~ ~ C_OO M O
N ~ N Et0 (-)-3-[4-[2-(2-Piperidinyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid (147 mg), dry methanol (5 ml) and magnesium hydroxide (8.72 mg) was added to 50 ml ~ne necked round bottom flask, fitted with a rilechanical stirrer and reflux condenser. The reaction mixture was refluxed at 80 °C for 12 h and monitored the progress of the reaction.
The reaction mixture was cooled to RT and distill off the methanol. The residue was washed with dry ether and dried under vacuum to afford pure magnesium salt of (-)-3-[4-[2-(2-morpholinyl-4-oxo-3,4-dihydroquinazolin-3 yl]ethoxy)phenyl]-2-ethoxypropanoic acid as a solid, (weighs about 100 m g, yield : 33.24 %, mp : 220 - 225 °C, purity 95.30 % by HPLC).
IR (I~Br) cm~l : 2933, 1674, 1610, 1584, 1566.
1H NMIZ (200 MHz, CI~C13) ~ : 8.12 (d, J=7.80Hz, 1H), 7.69 (t, J=4.00Hz, 1H), 7.53 (t, J=8.40Hz, 1H), 7.35 (t, J=7.SOHz, 1H), 7.13 (d, J=8.20Hz, 2H), 6.74 (d, J=8.OOHz, 2H), 4.54 (t, J = 4.90Hz, 2H), 4.31 (t, J=5.20Hz, 2H), 3.90 - 3.75 (m,.1H), 3.65 - 3.50 (m, 1H), 3.33 - 3.26 (m, 1H), 3.20 - 3.03 (m, 4H), 2.95 - 2.70 (m, 2H), 1.75 -1.50 (m, 6H), 1.10 -1.00 (m, 3H).
Example 15 (-)-3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxy propanoic acid metformin salt O -NH NH
O ~~ II
NCO ~ ~ C_O ~. ~ N~N~N.Me Et0 H Me (-)-2-EthoXy-3-[4-[2-(2-ethyl-4-axo-3,4-dihydro-3-quinazolinyl)ethoxy]
phenyl]propionic acid (2.0 g) and isopropanol (50 ml) was added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 45-55° for complete dissolution of the mass. Metformin (0.663 g).dissolved in isopropanol (10 ml) was .added to the reaction mixture of 75-85 °C for 5 h and monitor the progress of the reaction. The reaction mixture was cooled to room temperature and stirred for 12 h at room temperature. Distill off the isopropanol on rotavapor water bath at 45-55 °C under vacuum. The precipitated product was filtered, dried at 60 °C for 2-3 h to afford the pure metformin salt of (-)-3-[4-[2-(2-ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxy propanoic acid as off white crystalline solid, (weighs about 2.0 g, Yield : 77 %, m.p. 164-66 °C, purity 99% by HPLC).
IR as KBr shows the following absorption bands (cm 1) 3400-3300 (N-H
stretch), 3120 (-C-H aromatic), 2930 (-C-H aliphatic), 1660 (-COO stretch), 1587. (-CONH stretch), 1400 (-COO stretch).
1H NMR spectrum in I7MS0-d6 (TMS as internal standard) shows the following signals 8 8.13 (d, J=7.89Hz, 1H), 7.82 (t, ~J=7.01Hz, 1H), 7.64(d, J=8.21Hz, 1H), 7.50 (t, J= 7.26Hz, 2H), 7.13(d, J= 8.SOHz, 2H), 684 (d, J=B.SOHz, 2H), 4.47 (t, J=5.19Hz, 2H), 4.26 (t, J=5.19Hz, 2H), 3.99-3.84 (m, 1H), 3.60=3.40 (m, 1H), 3.40-3.20 (m, 1H), 3.06 (q, J= 6.96Hz, 2H), 2.88 (q, J= 6.64Hz, 2H), 2.8 (s, 6H), 1.32 (t, J= 7.17Hz, 3H), 1.02 (t, J= 6.96Hz, 3H).
The mass spectrum shows m/z, 411 (M+ + 1), 130 (C4H11N5), Anal. Calcd :
C23H2gNaO5; % C 60.11; % H : 6.86; % N 18.18; Found % C 59.89; % H 6.66;
N 18.00.

Example-lfi (-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin=6-yl)ethoxy]phenyl]-2-ethoxypropionic acid magnesium salt O _ NCO ~ ~ ~
C-O
N ~ I N Et0 Mg++

(-) ' 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimi'din-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), methanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and . reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. Magnesium hydroxide (0.328 g) was added to the reaction mixture at 60 °C in about minutes under stirring. Maintained gentle reflux of the reaction mixture for 14 hr and monitored the progress of the reaction. The reaction mixture was cooled t~ RT and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure magnesium salt of (-) 3-[4-[2-(1,5-dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as off white crystalline solid, (weighs about 4.09 g, yield : 80 %, rrip 113 °C, purity 99 by HPLC).
IR (KBr) cm 1 : 3120 (C-H aromatic), 2930 (-C-H aliphatic), 1693 (-COO / -CONH stretch), 1574 (-CONH amide-II band).
1H NMR (200 MHz, l~MSO-d6) 8 : 7.13 (d, J=8.3 Hz, 2Ii), 6.78 (d, J=8.3 Hz, 2H), 4.48 (t, T= 4.6 Hz, 2H), 4.35-4.15 (m, SH), 4.01-3.97 (m, 1H), 3.56-3.38 (m, 2H), 3.12-2.90 (in, 2H), 2.83 (t; J=7. Hz, 2H), 2.76 (s, 3H), 1.89-1.71 (m, 2H), 1.16 (t, J= 7.0 Hz, 3H), 0.98 (t, J= 7.3 Hz, 3H).

Mass m/z : 443 (M+ + 1), Anal. Calcd : C46HS8NsOloMg; % C 60.92; % H
6.40; % N 12.31; Found % C 60.80; % H 6.30; % N 12.20.
Example-17 (-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid potassium salt O _ O ~ / ~ ~ O
-C-O K
Et0 (-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), methanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. Potassium hydroxide (0.63 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to 1ZT and stirred for 2-3 h at room temperature. The precipitated product was filtered, vac~ium- dried to afford the pure potassium salt of (-) 3-[4-[2-(1,5-dimethyl-7-oxo-3-propyl-6, 7-dihydro=1 H-pyrazolo [4, 3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as off white crystalline solid (weighs about 4.6 g, yield : 85 %, mp : 168-170 °C, purity 99 % by HPL,C).
IR (KBr) cm-1 : 3120 (C-H aromatic), 2960 (-C-H aliphatic), 1690 (-COO I -CONK stretch), 1573 (-CONH amide-II band).
1H NMR (200 MHz, DMSO-d6) 8 : 7.13 (d, J=8.3 Hz, 2H); 6.78 (d, J=8.3 Iiz, 2H), 4.48 (t, J= 4.6 Hz, 2H), 4.35-4.15 (m, SH), 4.01-3.97 (m, 1H), 3.56-3.38 (m, 2H), 3.12-2.90 (m, 2H), 2.83 (t, J~7.8 Hz, 2H), 2.76 (s, 3H), 1.89-1.71 (m, 2H), 1.16 (t, J= 7.0 Hz, 3H), 0.98 (t, J= 7.3 Hz, 3H).
Mass mlz : 443 (M+ + 1), Anal. Calcd : Ca3Hz9N~OsK; % C 57.49; % H : 6.04;
N 11.66; Found % C 57.30; % H 5.9; % N 11.50.

Example-18 (-) 3-[4-[2-(1;5=Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-B-ethoxypropionic acid calcium salt ~ _ NCO ~ ~ 101 O
N ~ .
\ N~ Ca++
Et0 10 (-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimid~z-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), methanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. Calcium hydroxide 15 (0.418 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled , to RT and stirred for 2-3 h at room temperature. The precipitated product Was filtered, vacuum- dried to afford the pure calcium salt of (-) 3-[4-[2-(1,5-20 dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as off white crystalline solid (weighs about 4.17 g, yield : 80 %, mp : 251 °C (dec), purity 99 % by HPLC).
IR (KBr) cm 1 : 3150 (C-H aromatic), 2960 (-C-H aliphatic), 1690 (-COO / -CONH stretch), 1577 (-CONH amide II band).

1H NMR (200 MHz, DMSO-d6) 8 : 7.13 (d, J=8.3 Hz, 2H), 6.78 (d, J=8.3 Hz, 2H), 4.48 (t, J= 4.6 Hz, 2H), 4.35-4.15 (m, SH), 4.10-3.97 (m; 1H), 3.56-3.38 (m~ 2H), 3.12-2.90~(m, 2H), 2.83 (t, J=7.8 Hz, 2H), 2.76 (s, 3H), 1.89-1.71 (m, 2H), 1.16 (t, J= 7.0 Hz, 3H), 0.98 (t, J= 7.3 Hz, 3H).
Mass m/z : 443 (M+ + 1), Anal. Calcd : C46HssN8oioCa; % C 59.86; % H :
6.29; % 1V~ 12.14; Found % C 59.70; % H 6.15; % N 12Ø
Example-19 (-) , 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lithium salt O
NOD
Li N ~ I ~ Et -N
3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidiiz-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), methanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. Lithium hydroxide (0.47 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT
and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum- dried to afford the pure lithium salt of (-) 3-[4-[2-(1,5-dimethyl-7-oxo-3-propyl-6,7-dihydro-1 H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoXypropionic acid as off white crystalline solid (weighs about 4.3 g, yield : 85 %, mp : 254-266 °C, purity 99 % by HPLC).

IR (KBr) cm 1 : 3150 (C-H aromatic), 2950 (-C-H aliphatic), 1690 (-COO / -CONH stretch), 1574 (-CONH amide-II band).
1H NMIZ (200 MHz, DMSO-d6) 8 : 7.13 (d, J=8.3 Hz, 2H), 6.78 (d, J=8.3 Hz, 2H), 4.48 (t, J= 4.6 Hz, 2H), 4.35-4.15 (m, SH), 4.10-3.97 (m, 1H), 3.56-3.38 (m, 2H), 3.12-2.90 (m, 2H), 2.83 (t, J=7.8 Hz, 2H), 2.76 (s, 3H), 1.89-1.71 (m, 2H), 1.16 (t, J= 7,0 Hz, 3H), 0.98 (t, J= 7.3 Hz, 3H).
Mass m/z ~ : 443 (1VI+ + 1), Anal. Calcd : Ca3H29N4OsLi; % C 61.60; % H
6.47;%N12.49;Found%C61.45;%H6.31;%N12.35.
Example-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-ethoXypropionic acid sodium salt O _ NCO
N ~ ,--C-O Na Et0 (-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), methanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. Sodium hydroxide (0.45 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT
and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum- dried to afford the pure sodium salt of (-) 3-[4-[2-(1,5-dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as off white hygroscopic solid (weighs about 4.19 g, yield : 80 %, purity 99 % by HP1,C).
IR (I~Br) cm 1 : 3100 (C-H aromatic), 2963 (-C-H aliphatic), 1688 (-COO / - , CONH stretch), 1574 (-CONH amide-II band).
IH NMR (200 MHz, DMSO-d6) 8 : 7.13 (d, J=8.3 Hz, 2H), 6.78 (d, J=8.3 Hz, 2H), 4.48 (t, J= 4.6 Hz, 2H), 4.35-4.15 (m, 5H), 4.10-3.97 (m, 1H), 3.56-3.38 (m, 2H), 3.12-2.90 (m, 2H), 2.83 (t, J=7.8 Hz, 2H), 2.76 (s, 3H), 1.89-1.71 (m, 2H), 1.16 (t, J= 7.0 Hz, 3H), 0.981(t, J= 7.3 Hz, 3H).
Mass m/z : 443 (M++ 1).
Example-21 (-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid arginine salt O
NCO \-/ O O H NH2 C-O HN N
N ~ I ~ Et ~ H C02H
N ~NH3 (-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isopropanol (50 riml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. 1;-Argiriine (1.96 g) was added to the reaction mixture at 60° in about 10 minutes under stirring.
Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum-dried to afford the pure arginine salt of (-) 3-[4-[2-(1;5=dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as off white crystalline solid (weighs about 5.92 g, yield 85 %, mp : 192 °C, purity 99 % by HPLC).
IR (KBr) cm 1 : 3300-3200 (-NH stretch), 3150 (C-H aromatic), 2950 (-C-H
aliphatic), 1690 (-COO / -CONH stretch), 1583 (-CONH amide-II band).
1H NMR (200 MHz, DMSO-d6) 8 : 7.13 (d, J=8.3 Hz, 2H), 6.78 (d, J=8.3 Hz, 2H), 4.48 (t, J= 4.6 Hz, 2H), 4.35-4.15 (m, SH), 4.10-3.97 (m, 1H), 3.80 (m, 2H), 3.56=3.38 (m, 2H), 3.20 (m, 2H), 3.12-2.90 (m, 2H), 2.83 (t, J=7.8 Hz, 2H), 2.76 (s, 3H), 2.0-1.6 (m, 3H), 1.89-1.71 (m, 2H), 1.16 (t, J= 7.0 Hz, 3H), 0.98 (t, J= 7.3 Hz, 3H).
Mass xn/z : 443 (1VI+ + 1), Anal. Calcd : C2~H44N807i % ~ 56.49; % H : 7.14;
N 18.18; Found % C 56.34; % H 6.98; % N 17.99.
Example-22 (-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid 1t-(+) methyl benzylamine salt ,. ~ O
N ~C - C O NH3 N \ ( N ~ ~ C_O \ CHs EtO
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro=1H-pyrazolo[4,3-d]pyiimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isopropanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. R-(+) methyl benzylamine (1.36 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for - 14 hr and monitored the progress of the reaction. The reaction mixture vvas cooled to RT and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum- dried to afford the pure, hygroscopic (-) 3-[4-[2-(1,5-dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-5 yl)ethoxy]phenyl]-2-ethoxypropionic acid R-(+) methyl benzylamine salt as off white crystallixie solid (weighs about 5.41 g, yield : 85 %, mp : 114-°C~ pm'itY 99 % by HPI,C).
IR (KBr) crri 1 : 3150 (C-H aromatic), 2940 (-C-H aliphatic), 1687 (-COO / -CONH stretch), 1573 (-CONH amide-II band).
10 1H NMR (200 MHz, DMSO-d6) 8 : 7.40-7.20 (m, 5H), 7.13 (d, J=8.3 Hz, 2H), 6.78 (d, J=8.3 Hz, 2H), 4.48 (t, J= 4.6 Hz,. 2H), 4.35-4.15 (m, SH), 4.10 (m, 1H), 4.10-3.97 (m, 1H), 3.56-3.38 (m, 2H), 3.12-2.90 (m, 2H), 2.83 (t, J=7.8 Hz, 2H), 2.76 (s, 3H), 1.89-1.71 (m, 2H), 1.40 (d, 3H), 1.16 (t, J= 7.0 Hz, 3H), 0.98 (t, J= 7.3 Hz, 3H). , 15 Mass m/z : 443 (M+ + 1), tonal. Calcd : C31H41NSO5; % C 66.07; % H : 7.28;
N 12.43; Found % C 65.90; % H 7.15; % N 12.33.
Example-23 (-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H=pyrazolo(4,3-20 d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid S-(+)-~phenylglycinol salt O Ph N~~ ~ / ~ ~
N ~ C-O ~3N~OH
Et0 (-) 3-[4-[2-(1,5-Dimethyl-7-oxo=3-propyl-6,7-dihydro-1H-pyrazolo[4,3 d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isopropanol 25 (50 ml) ~,vere added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. S-(+)-phenylglycinol (1.549 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure S-(+)=phenylglycinol salt of (-) 3-[4-[2-( 1, 5-dimethyl-7-oxo-3-propyl-6, 7-dihydro-1 H-pyrazolo [4, 3-d]pyrimidin-yl)ethoxy]phenyl]-2-ethoxypropionic acid of the formula as off white hygroscopic solid (weighs about 5.23 g, yield : 80 %, purity 99 °l° by HPLC).
IR (KBr) cm 1 : 3400-3300 (O-H stretch), 3150 (C-H aromatic), 2950 (-C-H
aliphatic), 1689 (-COO / -CONH stretch), 1573 (-CONH amide-II band).
1H NMR (200 MHz, I~MSO-d6) ~ : 7.40 (m, SH), 7.13 (d, J=8.3 Hz, 2H), 6.78 (d, J=8.3 Hz, 2H), 4.48 (t, J= 4.6 Hz, 2H), 4.35-4.15 (m, SH), 4.10-3.97 (m, 1H), 4.00 (d, 2H), 3.60-3.50 (m, 1H), 3.56-3.38 (m, 2H), 3.12-2.90 (m, 2H), 2.83 (t, J=7.8 Hz, 2H), 2.76 (s, 3H), 1.89-1.71 (m, 2H), 1.16 (t, J= 7.0 Hz, 3H), 0.98 (t, J= 7.3 Hz, 3H).
Mass m/z : 443 (M+ + 1).
Example-24 (-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aminogeaanidine hydrogen carbonate salt O NW
NCO ~ ~ ~ ~ ,~ HCOO~
N ~ rC-O H3N N 3 Et0 Q H

(-) 3-[4-[2-(1,5-I7imethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionie acid (5.0 g), isopropanol (50 ml) were added to 250 ml four necked round bottom flask, gifted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °c for complete dissolution of the . mass. 1.53 g of Aminoguanidine hydrogen carbonate°was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum- dried to afford the pure aminoguanidine salt of (-) 3-[4-[2-(1,5-diinethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as off white hygroscope solid, (weighs about 5.5 g, yield : 85 %, mp : 110-112 °C, purity 99 % by Hl'LC).
IR (I~r) cm' : 3450-3350 (-NH stretch), 3150 (C-H aromatic), 2956 (-C-H
aliphatic), 1684 (-COO / -CONH stret'ch), 1572 (-CONH amide=II band).
1~I NMR (200~MHz, I~MSO-d6) 8 : 7.13 (d, J=8.3 Hz, 2H), 6.78 (d, J=8.3 Hz, 2H), 4.48 (t, J= 4.6 Hz, 2H), 4.35-4.15 (m, SH), 4.10-3.97 (m, 1H), 3.56-3.38 (m, 2H), 3.12-2.90 (W , 2H), 2.83 (t, J=7.8 Hz, 2H), 2.76 (s, 3H), 1.89-1.71 (m, 2H), 1.16 (t, J= 7.0 Hz, 3H), 0.98 (t, J= 7.3 Hz, 3H).
Mass m/z : 443 (M+ + 1).
Example-25 (-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo(4,3 d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid tromethamine s alt O OH
NCO ~ ~ ~ OH
rc_O
N ~ I N ~ Et0 N3N OH
(-) . 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isopropanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stiirer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. Trdmethamine (1.36 g) was added to the reaction mixture at 60 °C in about 10 minutes undei stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled,to RT and stirred for 2-3 h at room temperature. The precipitated product was filtered, aacuum- dried to afford the pure tromethamine salt of (-) 3-[4-[2-(1,5-dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic ~ acid as off white hygroscopic solid (weighs about 5.1 g, yield : 80 %, purity 99 % by HPLC).
IR (KBr) cmi 1 : 3300-3250 (O-H stretch), 3120 (C-Ii aromatic), 2950 (-C-H
aliphatic), 1689 (-COO / -CONH stretch), 1574 (-CONH, atiiide-II band).
1H NMR (200 MHz, DMSO-d6) 8 : 7.13 (d, J=8.3 Hz, 2H); 6.78 (d, J=8.3 Hz, 2H), 4.48 (t, J= 4.6 Hz, 2H), 4.35-4.15 (m, SH), 4.10-3.97 (m, 1H), 4.00 (s, 6H), 3.56-3.38 (m, 2H), 3.12-2.90 (m, 2H), 2.83 (t, J=7.8 Hz, 2H), 2.76 (s, 3H), 1.89-1.71 (m, 2H), 1.16 (t, J= 7.0 Hz, 3H), 0.98 (t, J= 7.3 Hz, 3H).
Mass m/z : 443 (M+ + 1).
Example-26 (-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4;3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid dicyclohexylamine salt O _ O ~N2 C-O
EtO
(-)-3-[4-[2-(1,5-I~imethyl)]-7-oxo-3-propyl-6,7-diliydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isopropanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass.
Dicyclohexylamine (2.04 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT
and 'stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure dicyclohexylamine salt of (-) 3-[4-[2-(1,5-dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3=d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as . off white crystalline solid (weighs about 5.6 g, yield : 80 %, mp : 132-134 °C, purity 99 % by HPLC).
IR (KBr) cm 1 : 3150 (C-H aromatic), 2950 (-C-H aliphatic), 1690 (-COO / -CONH stretch), 1574 .(-CONH amide-II band).
1H NMR (200 MHz, DMSO-d6) 8 : 7.13 (d, J=8.3 Hz, 2H), 6.78 (d, J=8.3 Hz, 2H), 4.48 (t, J= 4.6 Hz, 2H), 4.35-4.15 (m, 5H), 4.10-3.97 (rri, 1H), 3.56-3.38 (m, 2H), 3.12-2.90 (m, 2H), 2.83 (t, J=7.8 Hz, 2H), 2.76 (s, 3H), 2.60-1.00 (m, 22H)~, 1.89-1.71 (m, 2H), 1.16 (t, J= 7:0 Hz, 3H), 0.98 (t, J= 7.3 Hz, 3H).
Mass m/z : 443 (M++ 1), Anal. Calcd : C35Hs3NsOs; % C 67.41; % H : 8.5;
N 11.23; Found % C 67.25; % H 8.4; % N 11.15. ~., Example-27 (-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-5 octylglucamine salt O CH2-NH2-C$H~~
NCO ~ ~ 101 Etp C O H OH
N HO H
H OH
H OH

(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidill-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isopropanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a 10 mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. N-octylglucamine (3.31 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 h and monitored the progress of the reaction. 'fhe reaction mixture was cooled to 15 RT and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure N-octylglucamine salt of (-) 3-[4-[2-(1,5-dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)etlioxy]phenyl]-2-ethoxypropionic acid as off white hygroscopic solid (weighs about 6.6 g, yield : 80 %, purity 9'9 % by HPLC).
20 IR (KBr) cm 1 : 3350-3300 (O-H stretch), 3150 (C-H aromatic), 2930 (-C-H
aliphatic), 1689 (-COO / -CONH stretch), 1576 (-CONH amide-II band).
1H NMR (200 MHz, DMSO-d6) 8 : 7.13 (d, J=8.3 Hz, 2H)~ 6.78 (d, J=8.3 Hz, 2H), .4.48 .(t, J= 4.6 Hz, 2H), 4.35-4.1 S (m, SH), 4.20-3.01 (m, 8H), 4.01 (m, 1H), 4.10-3.97 (m, 1H), 3.56-3.38 (m,, 2H), 3.12-2.90 (rri, 2H), 2.83 (t, J=7.8 Hz, 2H), 2.76 (s, 3H), 1.89-1.71 (m, 2H), 1.42 -1.00 (m, 16H), 1.16 (t, J= 7.0 Hz, 3H), 0.98 (t, J= 7.3 Hz, 3H).
Mass m/z : 443 (M+ + 1).
Example-28 (-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)'ethoxy]phenyl]-2-ethoxypropionic acid N-methylglucamine salt O C H2-iV H2-C H3 N ~ ~ ~ O ~
H ' OH
C O
N~ Et0 H~ H
~. OH
H OH

(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro=1H-pyrazolo[4;3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isopropanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. 'The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. N-inethylglucamine (2.2 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT
and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum- dried to afford the pure, hygroscopic N-methylglucamine salt of (-) 3=[4-[2-(1,5-dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4;3-d]pyrirriidin-6-yl)ethoXy]phenyl]-2-ethoxypropionic acid as off white crystalline solid (weighs about 6.1 g, yield : 85 %, inp 115 °C, purity 99 % by HPLC).

IR (KBr) cm 1 : 3400-3200 (-OH stretch), 3150 (C-H aromatic), 2950 (-C-H
aliphatic), 1680 (-COO / -CONH stretch), 1 S74 (-CONH amide-TI band).
1H NMR (200 MHz, DMSO-d6) 8 : 7.13 (d, J=8.3 Hz, 2H), 6.78 (d, J=8.3 Hz, 2H), 4.48 (t, J= 4.6 Hz, 2H), 4.35-4.15 (m, SH), 4.10-3.97 (m, 1H), 4.00-3.26 S (m, 8H), 3.56-3.38 (m, 2H), 3.12-2.90 (m, 2H), 2.83 (t, J=7. Hz, 2H), 2.76 (s, 3H), 2.40 (s, 3H), 1.89-1.71 (m, 2H), 1.16 (t, J= 7,0 Hz; 3H), 0.98 (t, J= 7.3 Hz, 3H).
Mass m/z : 443 (M+ + 1), Anal. Calcd : C3oH47NsOlo; % C S6.S; % H : 7.37;
N 10.98; Found % C S6.3S; % H 7:25; % N 10.8.
Example-29 (-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-B-ethoxypropionic acid metformin salt O NH NH
N NCO \ / 101 ~ ~ N~N~N.NIe N , ~-c-~
Et0 H Me / .
1S (-) ' 3-[4-[2-(1,S-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isoproparol (SO ml) were added to 2S0 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to SS-60 °C for complete dissolution of the mass. Metformin free base (1.45 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was 'cooled to RT
and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure metformin salt of (-) 3-[4-[2-(1,S-2S dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3=d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as off white hygroscopic solid (weighs about 5.16g, yield : 80 %, purity 99 % by HPLC).
IR (KBr) cm 1 : 3400-3300 (N-H stretch), 3190 (C-H aromatic), 2968 (-C-H
aliphatic), '1687 (-COO / -CONH stretch), 1573 (-CONH amide-II band).
1H NMI~ (200 MHz, DMSO-d~) 8 : 7.13 (d, J=8.3 I-~z, 2H), 6.78 (d, J=8.3 Hz, 2H), 4.48 (t, J= 4.6 Hz, 2H), 4.35-4.15 (m, 5~I), 4.10-3.97 (rim, 1H), 3.56-3.38 (m, 2H), 3.12-2.90 (m, 2H), 2.90 (s, 6H), 2.83 (t, 3=7.8 Hz, 2H), 2.76 (s, 3H), 1.89-1.71 (m, 2H), 1.16 (t, J= 7.0 Hz, 3H), 0.98 (t, J= 7.3 Hz, 3H).
Mass m/z : 443 (M++ 1).
example-30 (-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lysine salt O O
NCO ~ l o ~ NH3 N ~ I . i Et ~C-O ~ (CH2)a.
N
H--~-N H2 COON
(-) , 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydr'o-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isopropanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. Lysine monohydrate free base (1.65 g) was added to the reaction mixture at 60 °C in about minutes under stirring. Maintained gentle reflux of the reaction mixture for 14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure lysine salt of (-) 3-[4-[2-(1,5-dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as off white crystalline solid (weighs about 5.98 g, yield : 90 %, mp : 158-160 °C, purity 99 % by HPLC).
IR (I~r) cm 1 : 3400-3300 (N-H stretch), 3150 (C-H aroW atic), 2950 (-C-H
aliphatic), 1694 (-COO / -CONH stretch), 1573 (-CONH amide-II band).
1H NMR (200 MHz, DMSO-d6) 8 : 7.13 (d, J=8.3 Hz, 2H), 6.78 (d, J=8.3 Hz, 2H), 4.48 (t, J= 4.6 Hz, 2H), 4.35-4.15 (m, SH), 4.20 (t, 1H); 4.1-3.97 (m, 1H), 3.56-3.38 (m, 2H), 3.12-2.90 (rim, 2H), 3.01 (t, 2H), 2.83 (t, J=7.8 Hz, 2H), 2.76 (s, 3H), 2.20-1.5 (m, 6H), 1.89-1.71 (m, 2H), 1.16 (t, J= 7.0 Hz, 3H), 0.98 (t, J= 7.3 Hz, 3H).
Mass m/z : 443 (M+ + 1), Anal. Calcd : C29H44N6O7; % C 59.18; % H : 7.46;
N 14.78; Found % C 59.0; % H 7.29; % N 14.59:
(-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-lI-I-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid was prepared according .to the procedure described in our copending IJS patent application No. 09/507,373 [2S, N(1S)]-2-Ethoxy-3-[4-[2-(5-ethyl-1-methyl-7-oxo-3-propyl-6,7-dihydro-1 H-pyrazolo [4, 3-d]pyrimidin-6-y] ethoxy]phenyl]-N-(2-hydroxy-1-phenylethyl)propanamide was taken, in a mixture of dioxarie, water and 1M
sulfuric acid at room temperature and stirred under reflux for 34 h. Water and dioxane were removed under vacuum. The residue was taken in water and extracted with ethyl acetate and the ethyl acetate layer was washed with water, dried (Na2S04) and evaporated to dryness to yield the crude compound. The crude compound was purified by column chromatography using 50 % ethyl acetate in pet. ether as an eluent to afford (-)-3-[4-[2-(1-methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2- .
ethoxypropionic acid.

However, any other procedure for preparing (-)-3-[4-[2-(1-methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1 H-pyrazolo [4, 3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid can be used. (~) 3-[4-[2-(1-methyl-5-ethyl-7-oxo-3-propyl-6, 7-dihydro-1 H-pyrazolo [4, 3-d]pyrimidin-6-yl) 5 ethoxy]phenyl]-2-ethoxypropionic acid and (+)-3-[4-[2-(1-methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[~.,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid can be prepared by a similar procedure described above.
10 Example-31 (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid magnesium salt O
C-O
Et0 Mg++
(-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
15 pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), methanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass and magnesium hydroxide (0.29 g) was added to the reaction mixture at 60 °C in about 20 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to ' RT and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure magnesium salt of (-)-3-[4-[2-(1-methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3- .
25 d]pyrimidin-6-yl)ethoxy] phenyl]-2-ethoxypropionic acid as off white crystalline solid, (weighs about 4.0 g, yield : 80 %, purity f9 % by HPLC). .

IR (KBr) crri 1 : 3120 (C-H aromatic), 2970 (-C-T~ aliphatic), 1688 (-COO l -CONH stretch), 1576 (amide-II band).
1H NMR (200 MHz, DMSO-d6) 8 : 7.13 (d, J=8.4 Hz, 2H), 6.77 (d, J=8.6 Hz, 2H), 4.50 (t, J= 5.0 Hz, 2H), 4.29-4.22 (m, 5H), 4.01 (t, J=3.7 Hz, 1H), 3.69-~ 3.35 (m, 2H), 3.10-2.94 (m, 4H), 2.84 (t, J=7.5 Hz, 2H), 1.90-1.78 (m, 2H), 1.30 (t, J= 7.0 Hz, 3H), 1.16 (t, J=7.4 Hz, 3H), 0.97 (t, J= 7.4 Hz, 3H).
Mass m/z : 457 (M+ + 1), Anal. Calcd : C4gH6zN8~IOMg~ % C 61.67; % H :
6.63; % N 11.99; Found % C 61.58; % H 6.55; % N 11.84.
Example-3B
(-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7=dihydro-1~I-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid potassium salt O
O
-C-O K
Et0 (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1I-I-pyrazolo[4,3-d]
15. pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isopropanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. Potassium hydroxide (0.61 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT
and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure potassium salt of (-)-3-[4-[2-(1-methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d] pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as off white ainoiphous solid, (weighs about 4.35 g, yield : 80 %, mp : 164 °C, purity 99 % by HPLC).
IR (It.Br) cm 1 : 3120 (C-H aromatic), 2970 (-C-H aliphatic), 1681 (-COO / -C~NH stretch), 1576 (amide-II band).
1H NMR (200 MHz, DMSO-d6) ~ : 7.13 (d, J=8.4 Hz, 2H), 6.77 (d, J=8.6 Hz, 2H), 4.50 ,(t, J= ~.0 Hz, 2H), 4.29-4.22 (rim, SH),-4.01 (t, J=3.7 Hz, 1H), 3.69-3.35 (m, 2H), 3.10-2.94 (m, 4H), 2.84 (t, J=7.5 Hz, 2H), 1.90-1.78 (m, 2H), 138 (t, J= 7.3 Hz, 3H), 1.16 (t, J=7.0 Hz, 3H), 0.97 (t, J= 7.4 Iiz, 3H).
Mass spectrum shows m/z : 457 (M+' + 1), Anal. Calcd : Ca4H31N405R~
°a C
58.29; % H : 6.27; % N 11.33; Found % C 58.1; % H 6.15; % N 11.20.
lJxariiple-33 .
(-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid calcium salt . N NBC \ .~ ~ ~
C-O
Et0 Ca++

(-)-3-[4-[2-( 1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1 H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), methanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and ~ reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. Calcium hydroxide (0.81 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT
and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure calcium salt of (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d] pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic ~ acid as off White solid, (weighs about 4.4 g, yield : 85 %, mp : >260 °C, purity 99 % by HPLC).
IR (KBr) cm 1 : 3120 (C-H aromatic), 2970 (-C-H aliphatic), 1681 (-COO l -CONH stretch), 1576 (-CONH stretch).
1H NMR (200 MHz, DMSO-d6) 8 : 7.13 (d, J=8.4 Hz, 2H), 6.77 (d, J=8.6 Hz, 2H), 4.50 (t, J= 5.0 Hz, 2H), 4.29-4.22 (m, SH), 4.01 (t, J=3.7 Hz, 1H), 3.69-3.35 (m, 2H), 3.1-2.94 (m, 4H), 2.84 (t, J=7.3 Hz, 3H), 1.90-1.78 (m, 2H), 1.38 (t, J= 7.3 Hz, 3H), 1.16 (t, J=7.0 Hz, 3H), 0.97 (t, J= 7.4 IIz, 3H).
Mass m/z : 457 (M+ + 1), Anal. Calcd : C48H62N$OloCa; % C 60.63; % H
6.52; % N 11.78; Found % C 60.51; % H 6.4; % N 11.60.
Example-34 (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lithium salt O
N NCO \ . / 101. O
N ~ ,--O_~ a Et0 i (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-ethoXypropionic acid (5.0 g), methanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. Lithium hydroxide (0.44 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT

and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure lithium salt of (-)-3-[4-[2-(1-methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d] pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as ~ off white amorphous solid, (weighs about 4.55 g, yield : 90 %, mp : 215-218 °C, purity 99% by HPLC).
IR (KBr) cm 1 : 3120 (C-H aromatic), 2857 (-C-H aliphatic), 1686 (-COO / -CONH stretch), 1570 (amide-II band).
1H NMR (200 MHz, I7MSO-d6) 8 : 7.13 (d, J=8.4 Hz, 2H), 6.77 (d, J=8.6 Hz, 2H), 4.50 (t, J= 5.0 Hz, 2IY), 4.29-4.22 (m, SH), 4:01 (t, J=3.7 Hz, lI~), 3.69 3.35 (m, 2H), 3.1-2.94 (m, 4H), 2.84 (t, J=7.5 Hz, 2H), 1.90-1.78 (m, 2H), 1.38 (t, J= 7.3 Hz, 3H), 1.16 (t, J=7.OHz, 2H), 0.9'7 (t, J= 7.4 Hz, 3H).
Mass m/z : 457 (M+ + 1), Anal. Calcd : C24H3iN40sLi; % C 62.33; % H :
6.70;. % N 12.12; Found % C 62.1; % H 6.58; % N 12.10 Example-35 (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo (4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid sodium salt O
0 \ / ~ ~ N~ ._ C-O
Ef0 (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), methanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. Sodium hydroxide (0.43 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT
and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure sodium salt of (-)-3-[4-[2-(1-methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d] pyrimidin-6-5 yl)ethoxy]phenyl]-2-ethoxypropionic acid as off white amorphous solid, (weighs about 4.25 g, yield : 80 %, mp : 112-114 °G, purity 99 % by HPLC).
IR (I~.Br) cm 1 : 3120 (C-H aromatic), 2970 (-C-H aliphatic), 1680 (-COO / -CONH stretch), 1570 (amide-II band).
1H NMR (200 MHz, DMSO-d6) 8 : 7.13 (d, J=8.4 Hz, 2H); 6.77 (d, J=8.6 Hz, 10 2H), 4.50 (t, J= 5.0 Hz, 2H), 4.29-4.22 (m, SH), 4.01 (t, J=3.7 Hz, 1~I), 3.69-3.35 (rim; 2H), 3.10-2.94 (m, 4H), 2.84 (t, J=7.5 Hz, 2H), 1.90-1.78 (m; 2H), 1.16 (t, J= 7.0 Hz, 3H), 1.38 (t, J= 7.3 Hz, 3H), 0.97 (t, J= 7.4 Hz, 3H).
Mass mlz : 457 (M+ + 1), Anal. Calcd : Ca4H31N4O5Na; % C 60.25; % H
6.48;%N11.71;Found%C60.15;°/.°H6.31;%N11.58.
Example=36 (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H=pyrazolo [4,3=
d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid arginine salt p _ N~~ ~ I O ~ HN N NH2 N ~ ( N ~ Et~ C O H C~2H
~NH3 (-)-3-[4-[2-( 1-Methyl-5-ethyl-7-oxo-3 -propyl-6,7-dihydro-1 H-pyrazolo [4, 3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic . acid (5.0 g), isopropanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the rr~ass. L-Arginine (1.9 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring.
Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure arginine salt of (-)-3-[4-[2-(1-methyl-5-ethyl-7-oxo-propyl-6;7-dihydro-1H-pyrazolo[4,3-d] pyrimidin-6-yl)ethoxy]phenyl]-2 ethoxypropionic acid as off white amorphous solid, (weighs about 5.5 g, yield 80 %, mp : 235 °C, purity 99 % by HPLC).
IR (KBr) , cm 1 : 3360 (-NH stretch), 3120 (C-H aromatic), 2957 (-C-H
aliphatic), 1688 (-COO / -CONH stretch), 1573 (amide-II band).
1H NMR (200 MHz, I~MSO-d6) 8 : 7.13 (d, J=8.4 Hz; 2H),'6.77 (d, J=8.6 Hz, 2H), 4.50 (t, J= 5.0 Hz, 2H), 4.29-4.22 (m, SH), 4.01 (t, J=3.7 Hz, 1H), 3.80 (m, 2H), 3.69-3.35 (m, 2H), 3.20 (m, 3H), 3.10-2.94 (m, 4H), 2.84 (t, J=7.5 Hz, 2H), 1.90-1.78 (m, 2H), 1.60-2.00 (m, 3H), 1.38 (t, J= 7.3 Hz, 3H), 1.16 (t, J= 7.0 Hz, 3H), 0.97 (t, J= 7.4 Hz, 3H).
Mass m/z : 457 (M+ + 1), Anal. Calcd : C3oH4gN807; % C 57.14; % H : 7.3;
N17.75;Found%C57;%H7.15;%N17.58.
Example-37 (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid R-(+) methyl benzylamine salt O
O ~ ~ ~ 0 NH3 C-O
~EtO ~
(-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydio-1H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isopropanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. R-(+) methyl benzylamilie (1.32 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure, hygroscopic (-)-3-[4-[2-( 1-methyl-5-ethyl-7-oxo-3-propyl-6, 7-dihydro-1 H-pyrazolo [4, 3 -d]pyrimidin~
6-yl)ethoxy] phenyl]-2-ethoxypropionic acid R-(+) methyl benzylamine salt as off white solid, (weighs about 4.4 g, yield : 70 %, mp : 164-166 °C, purity 99 % by HPLC).
IR (KDr) cm 1 : 3120 (C-H aromatic), 2970 (-C-H aliphatic), 1689 (-COO / -CONH stretch), 1573 (amide-II band).
1H NMR (200 MHz, DMSO-d6) b : 7.20 -7.40 (m, SH), 7.13 (d, J=8.4 Hz, 2H), 6.77 (d, J=8.6 Hz, 2H), 4.50 (t,']= 5.0 Hz, 2H), 4.29-4.22 (m, SH), 4..10 (m, 1H), 4.01 (t, J=3.0 Hz, 1H), 3.69-3.35 (m, 2H), 3.10-2.94 (m, 4H), 2.84 (t, J=7.5 Hz, 2H), 1.90-1.78 (m, 2H), 1.40 (d, 3H), 1.16 (t; J= 7.0 Hz, 3H), 1.38 (t, J= 7.3 Hz, 3H), 0.97 (t, J= 7.4 Hz, 3H). . . _ Mass m/z : 457 (M++ 1).
Example-38 (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-lI3-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid S-(+)-phenylglycinol salt O Ph N. NCO ~_~ ~ O
C-O H3N~OH
EtO O
(-)-3-[4-[2-( 1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1 H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isopropanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. 'lie reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. S-(+)-1'henylglycinol ( 1.5 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT
and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure S-(+)-phenylglycinol salt of (-)-3-[4-[2-(1-methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[43-d]
pyririzidili-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as off white crystalline solid, (weighs about 5.5 g, yield : 85 %, mp : 88-90 °C, purity 99 % by HPLC).
IR (KBr) cm 1 : 3150 (C-H aromatic), 2950 (-C-H aliphatic), 1686 (-CQO / -CONH stretch), 1570 (amide-II band).
The 1H NMR (200 MHz, I~MS~-d6) 8 : 7.40 (m, 5H), 7.13 (d, J=8.4 Hz, 2H), 6.77 (d, J=8.6 Hz, 2H), 4.50 (t, J-- 5.0 Hz, 2H), 4.29-4.22 (m, 5H), 4.10 (in, 1H), 4.01 (t, J=3.70 Hz, 1H), 4.00 (d, 2H), 3.60-3.80 (m, 1H), 3.69-3.35 (in, 2H), 3.10-2.94 (m, 4H), 2.84 (t, J=7.5 Hz, 2H), 1.90-1.78 (in, 2H), 1.38 (t, J=
7.3 Hz, 3H), 1.16 (t, J= 7.0 Hz, 3H), 0.97 (t, J= 7.4 Hz, 3H), Mass m/z : 457 (M+ + 1), Anal. Calcd : C32H43N5~6~ % C 64.59; % H : 7.15;
N 11.80; Found % C 64.59; % H 7.15; % N 11.66.

Example-39 (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aminoguanidine hydrogen carbonate salt O _ NH
N NCO \ _ / 101 ~ ~ ,~ 3 HCOO~

N ~ I N Et0 ~ H
(-)-3-[4-[2-( 1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro- l I~-pyrazolo [4, 3-d]
pyrimidiil-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isopropanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. Aminoguanidine hydrogen carbonate (1.49 g) was added to the reaction mixture at 60 °O
in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT and stirred for 2-3 h at room temperature. The precipitated product was filtered, Vacuum dried to afford the pure aminoguanidine hydrogen carbonate salt of (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as off white crystalline solid, (weighs about 5.2 g, yield : 80 %, mp : 130 °C, purity 99% by HPLC).
IR (I~Br) cm 1 : 3450-3350 (-NH stretch), 3120 (C-H aromatic), 2970 (-C-H
aliphatic), 1676 (-COO / -CONH stretch), 1573 (amide-II band).
1H NMR (200 MHz, DMSO-d6) 8 : 7.13 (d, J=8.4 Hz, 2H), 6.77 (d, J=8.6 Hz, 2H), 4.50 (t, J= 5.0 Hz, 2H), 4.29-4.22 (m, 5H), 4.01 (t, J=3.70 Hz, 1H), 3.69 3.35.(m, 2H), 3.10-2.94 (m, 4H), 2.84 (t, J=7.5 Hz, 2H), 1.90-1.78 (m, 2H), 1.38 (tJ= 7.3 Hz, 3H), 1.16 (t, J= 7.0 Hz, 2H), 0.97 (t, J= 7.4 Hz, 3H).

Mass m/z : 457 (M+ + 1), Anal. Calcd : C26H~oN80~; % C 54.16; % H : 6.94;
N 19.44; Found % C 54.00; % H 6.78; % N 19.32.
Example-40 5 (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]p~rimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid tromethamine s alt O OH
N ~0 \ / ~ C~ OH
O O
Et0 H3~
OH
(-)-3-[4-[2-( 1-Methyl-5-ethyl-7-oxo-3-propyl-6, 7-dihydro-1 H-pyrazolo [4, 3-d]
10 pyrimidin=6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isopropanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. Tromethamine (1.32 g) was added to the reaction mixture at 60 °C in about 10 minutes under 15 stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to I~T
and stirred for 2-3 ,h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure tromethamine salt of (-)-3-[4-[2-(1-methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-20 yl)ethoxy]phenyl]-2-ethoxypropionic acid as off white crystalline solid, (weighs about 5.18 g, yield : 82 %, mp : 116-118 °C, purity 99 % by HPLC).
IR (KBr) cni 1 : 3300-3250 (-OH stretch), 3120 (C-H aromatic), 2935 (-C-H
aliphatic), 1693 (-COO / -CONH stretch), 1575 (amide-II band).
1H NMR (200 MHz, DMSO-d6) 8 : 7.13 (d, J=8.4 Hz, 2H), 6.77 (d, J=8.1 Hz, 25 2H), 4.50 (t, J= 5.0 Hz, 2H), 4.29-4.22 (m, 5H), 4.01 (t, J=3.70 Hz; 1H), 4.00 (s, 6H), 3.69-3.35 (m, 2H), 3.10-2.94 (m, 4H), 2.84 (t, J=7.5 Hz, 2H), 1.90-1.78 (m, 2H), 1.38 .(t, J= 7.3 Hz, 3H), 1.16 (t, J= 7.0 Hz, 3H), 0.97 (t, J=
7.4 Hz, 3H). , Mass m/z : 457 (M+ + 1), Anal. Calcd : CZgHa3N30g; % C 61.20; % H : 7.83;
% N 7.65; Found % C 61.05; % H 7.70; % N 7.50.
Example-41 (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-lA-pyrazolo [4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid dicyclohexylamine salt O
N NCO ~-~ O O O+ N2, C-O
N ~ I N~ Et0 i (-)-3-[4-[2-( 1-Methyl-5-ethyl-7-oxo-3~propyl-6,7-dihydro-1 H-pyrazolo[4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isopropanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflex condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass.
Dicyclohexylamine (1.98 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflex of the reaction mixture for 12-14 hr and monitored the.progress of the reaction. The reaction mixture was cooled to RT
and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure dicyclohexylamine salt of (-)-3-[4-[2-(1-methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as off white crystalline solid, (weighs about 5.51 g, yield : 79 %, mp : 138-140 °C, purity 99% by HPLC.

1R (KBr) cxri 1 : 3150 (C-H aromatic), 2933 (-C-H aliphatic), 1682 (-COO / -CONH stretch), 1571 (amide-II band).
1H NMR (200 MHz, DMSO-d6) 8 : 7.13 (d, J=8.4 Hz, 2H), 6.77 (d, J=8.6 Hz, 2H), 4.50 (t, J= 5.0 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=7.5 Hz, 2H), 2.60-1.00 (m, 22H), 1.90-1.78 (m, 2H), 1.38 (t, J= 7.3 Hz, 3H), 1.16 (t, J= 7.0 Hz, 3H), 0.97 (t, J=
7.4 Hz, 3H).
Mass m/z : 457 (M+ + 1), Anal. Calcd : C36HSSNSOSi % C 67.81; % H : 8.63;
N 10.98; Found % C 67.65; % H 8.55; % N 10.75.
example-42 (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro'-1H-pyrazolo [4,3-d]pyrirriidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-octylglucamine salt O C H~-N H2-C$H~ ~
NCO ~ ~ 101 O H ' OH
N ~ I ~ rC-O . HO H
N Et0 H' OH
H ' OH
1~ CH~OH
(-)-3-[4-[2-( 1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]
pyriinidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isopropanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. N-octylglucamine (3.2 g) was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of, the reaction mia~ture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT
and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure, hygroscopic N=octylglucamine salt of (-)-3-[4-[2-(1-methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as off white hygroscopic solid, (weighs about 6.48 g, yield : 79 %, purity 99 % by HPLC.
IR (KBr) cm 1 : 3350 (-OH stretch), 3150 (C-H aromatic), 2929 (-C-H
aliphatic), 1689 (-COO / -CONH stretch), 1575 (amide-II band).
1H NMR (200 MHz, DMSO-d6) b : 7.13 (d, J=8.4 Hz, 2H), 6.77 (d, J=8.6 Hz, 2H), 4,50 (t, J= 5.0 Hz, 2H), 4.29-4.22 (m, 5H), 4.01 (t, J=3.70 Hz, 1H),4.20-3.06 (m, 8H), 3.69-3.35 (m, 2H), 3.10-2.94 (m, 4H), 2.84 (t~ J=7.5 Hz, 2H), 1.90-1.78 (m, 2H), 1.40-1.00 (m, 16H), 1.38 (t, J= 7.3 Hz, 3H), 1.16 (t, J=
7.0 Hz, 3H), 0.97 (t, J= 7.4 Hz, 3H).
Mass m/z : 457 (NT~ + 1).
Example-43 (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-lI3f-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid ~hT-methylglucamine salt .

O ~, H OH
N ~ ~ ~ rC-O HO H
Et0 H OH
H OH

(-)-3-[4-[2-( 1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1 H-pyrazolo [4,3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropioriic acid (5.0 g), isopropanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. N-methylglucamine (2.1g) of was added to the reaction mixture at 60 °C in about 10 minutes under stirring. Maintained gentle reflux of the reaction mixture for 12-14 hr. and monitored the progress of the reaction. The reaction mixture was cooled to RT
and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum dried to afford the pure, hygroscopic N-methylglucamine salt of (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxa-3-propyl-6,7-dihydro-1H-pyrazolo[4,3- ' d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as off crystalline hygroscopic solid, (weighs about 5.7 g, yield : 80 %, purity 99 % by HPLC).
IR (KBr) cm 1 : 3400-3300 (-OH stretch), 3150 (C-H aromatic), 2935 (-C-H
aliphatic), 1676 (-COO / -CONH stretch), 1576 (amide-II band).
1H NMR (200 MHz, DMSO-d6) 8 : 7.13 (d, J=8.4 Hz, 2H); 6.77 (d, J=8.6 Hz, 2H), 4.50 (t, J= 5.0 Hz, 2H), 4.29-4.22 (m, SH), 4.01 (t, J=3.70 Hz, 1H),4.00-3.26 (m, 8H), 3.69-3.35 (m, 2H), 3.10-2.94 (m, 4H), 2.84 (t, J=7.5 Hz, 2H), 2.40 (s, 3H), 1.90-1.78 (m, 2H), 1.38 (t, J= 7.3 Hz, 3H), 1.16 (t, J= 7.0 Hz, 3H), 0.97 (t, J= 7.4 Hz, 3H).
Mass m/z : 457 (M++ 1).
Example-44 (-)-3-(4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo [4,3-d] pyrimidin-6-yl)ethoxy]phenyl]-2~ethoxypropionic acid metformin salt NH NH
i O
N N~~O \ / o O ~ ~ ~L .Me --C-O . H3N N N
~ N~ Et0 H Me (-)-3-[4-[2-( 1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1 H-pyrazolo [4, 3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isopropariol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly heated to 55-60 °C for complete dissolution of the mass. Metformin (1.41 g) as free base was added to the reaction mixture at 60 °C in about 10 minutes under stiiTing. Maintained gentle reflux of the reaction mixture for 12-14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT and stirred for 2-3 h at room temperature. The precipitated product was 5 filtered, vacuum dried to afford the pure, crystalline metformin salt of (-)-3-[4-[2-(1-methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as off white crystalline solid, (weighs about 5.45 g, yield : 85 %, rnp : 118 °C, purity 99 by HPLC). ' 10 IR (KBr) cm 1 :) 3350 (-OH stretch), 3150 (C-H arorizatic), 2950 (-C-H
aliphatic), 1677 (-COO / -CONH stretch), 1574 (amide-II band).
1H NMR (200 MHz, DMSO-d6) ~ : 7.13 (d, J=8.4 Hz, 2H), 6.77 (d, J=8.6 Hz, 2H), 4.50 (t, J= 5.0 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), 2.90 (s, 6H), 2.84 (t, J=7.5 Hz, 2H), 1.90-15 1.78 (m, 2H), 1.38 (t, J= 7.3 Hz, 3H), 1.16 (t, J= 7.0 Hz, 3H), 0.97 (t, J=
7.4 Hz, 3H).
Mass m/z : 457 (M++ 1). Anal. Calcd : C2gH43N9Os; % C 57.43; % H : 7.35;
N 21.53; Found % C 57.29; % H 7.25; % N 21.40.
20 Example-45 ' (-)-3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-lI3-pyrazolo [4,3-d] pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid Lysine salt O _ 0 NCO ~ ~ o ~ ~ H3 Et0 C O . (CH2)a.

COOH

(-)-3-[4-[2-( 1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1 H-pyrazolo [4, 3-d]
pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid (5.0 g), isopropanol (50 ml) were added to 250 ml four necked round bottom flask, fitted with a mechanical stirrer and reflux condenser. The reaction mixture was slowly S heated to 55-60 °C for complete dissolution of the mass. Lysine monohydrate (1.79 g) free base was added to the reaction mixture at 60 °C in about minutes under stirring. Maintained gentle reflux of the reaction mixture for 14 hr and monitored the progress of the reaction. The reaction mixture was cooled to RT and stirred for 2-3 h at room temperature. The precipitated product was filtered, vacuum- dried to afford the pure lysine salt of (-)-3-[4-[2-(1-methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid as off white amorphous solid, weighs about 5.77 g, yield : 85 %, mp : 162-164 °C, purity 99 % by HPLC).
IR (KBr) em 1 : 3120 (C-H aromatic), 2965 (-C-H aliphatic), 1691 (-COO l -CONH stretch), 1573 (amide-II band).
1H NMR (200 MHz, DMSO-d6) 8 : 7.13 ,(d, J=8.4 Hz, 2H), 6.77 (d, J=8.6 Hz, 2H), 4.50 (t, J= 5.4 Hz, 2H), 4.29-4.22 (m, SH), 4.20 (t, 1H), 4.01 (t, J=3.70 Hz, 1H), 3.69-3.35 (m, 2H), 3.10 (t, 2H), 3.10-2.94 (m, 4H), 2.90 (s, 6H), 2.84 (t, J=7.5 Hz, 2H), 2.11-1.5 (m, 6H), 1.90-1.78 (m, 2H), 1.38 (t, J= 7.3 Hz, 3H), 1.16 (t, J= 7.0 Hz, 3H), 0.97 (t, J= 7.4'Hz, 3H).
Mass m/z ; 457 (M+ + 1). Anal. Calcd : C3oH48N6O8; % C 58.06; % I~ : 7.74;
N 13.54; Found % C 57.9; % H 7.55; % N 13.38.
(-) .2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoXy]phenyl]propanoic acid was prepared according to the procedure described in our copending application No. 09/507,371 :

A solution of [2S, N(1S)]-2-ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]-N-(2-hydroxy-1-phenylethyl) propanamide (295 mg, 0.53 inmol) in a mixture of 1M sulfuric acid. (7.7 mL) and dioxane / water (1 : 1, 14 mL) was heated at 90 °C for 48 h and the phi of the mixture was adjusted to 4 by the addition of aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate and the combined ethyl acetate layers were washed with water, brine, dried (NazS04) and evaporated to yield (-) 2-ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid as a colorless solid.
~Iowever, any other procedure for preparing (-) 2-ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid can be used. (~) 2-ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid and (+) 2-ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid can be prepared by a similar procedure described above. .
Example 46 (-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid potassium salt O
Ph N~ j , O
N\/\ \ I H OC2H5 O
A mixture of (-) 2-ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid (5.0 g) and isopropanol (75 ml) was refluxed to obtain clear solution. Aqueous potassium hydroxide solution (0.63 g in 2 ml water) was added slowly at refluX temperature under stirring and continued stirring for 2-3 h. Then the reaction mass was cooled~to room temperature and continued stirring for further 12 h. The precipitated solid. was filtered and dried to yield the title compound, (weights about 4.5 g, mp (DSC) 240.9 °C).
1R (KBr) cni 1 . 3439.8, 2976.2, 2934.3, 2877:4, 1667.1, 1602.7, 1551.4, 1509.9, 1448.7, 1407.3, 1363.2, 1241.8,1178.2, 1108.7, 957.9, 898.3, 864.2, 815.7, 781.9, 696.6, 643.6.
p- XRD: 5.56, 7.46, 8.30, 14.36, 14.72, 15.74, 16.84, 17.06, 17.88, 18.40, 18.68, 19.44, 24.30, 24.42, 24.92 (2A).
Exariiple 47 (-) 2-Ethoxy-3-(4-[2-[2-ethyl-6-oxo-4-phenyl-1,6=dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid sodium salt O
Ph [ N~ , I '. O
O ~" H OC2H5 O
1~ mixture of (-) 2-ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-ylJethoxy]phenylJpropanoic acid (5.0 g) and isopropanol (75 ml) was refluxed to obtain clear solution. Sodium methoXide (0.615g) v~ias added at reflux temperature under stirring and continued stirring for 5-6 h.
Then the reaction mass was cooled to room temperature, filtered and dried to yield the title compound (weights about 4.6 g, mp (DSC) 251.19 °C).
IR (KBr) cm 1 : 3437.2, 2977.7, 2879.1, 1667.7, 1605.4, 1552:5, 1509.7, 1449.0, 1407.6, 1362.9, 1282.8, 1242.0, 1178.2, 1108.9, 1047.4, 958.6, 898.9, 863.4, 815.4, 781.3, 737.5, 696.1, 644.,6, 519Ø
p- XRD: 5.52, 7.38, 8.24, 14.42, 14.68, 17.0, 17.88, 19.46, 19.80, 23.38, 24.26, 24.44, 26.40 (2~).

Example 48 (-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid L-arginine salt P h I N~~ / I , O ~ H N N ~~
N~ ~ H OC2H5 ~ H C02H
O O+ NH3 A , mixture of (-) 2-ethoxy-3-r4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid (10 g) and isopropanol (200 ml) was refluxed to obtain clear solution. Aqueous L arginine solution (3.99 g in 6 ml water) was added slowly at reflux temperature under stirring and continued stirring for 2-3 h. Then the reaction mass was cooled to room temperature and continued stirring for further 12 h. The precipitated solid was filtered and dried to yield the title compound (weights about 8.5 g, mp (DSC) 187 °G).
IR (hBr) cni 1 : 3358.9, 3064.4, 2974.3, 1665.5, 1591.0, 1544.9, 1511.2, 1448.9, 1406.3, 1323.7, 1240.1, 1178.9, 1111.2, 1046.2, 956.8, 896.7, 780.5, 697.3, 542:0.
p- XRD: 3.68, 7.34, 11.34, 12.74, 14.18, 14.86, 15.12, 16.64, 19.48, 20.0, 20.54, 20.86, 22.70, 30.02 (20).
Example 49 (-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-g,fi-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid L-lysine salt O

Ph I N~ / [ ' O0 (CH2)4 N~ ~ H OC2H5 H-~--NH2 O
O COOH

A mixture of (-) 2-ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid (5.0 g) and isopropanol (75 ml) was refluxed to obtain clear solution. Aqueous L lysine solution (1.88 g in 3m1 water) was added slowly at reflux temperature under stirring and 5 continued ~ stirring for 12-15 h. Then the reaction mass was cooled to room temperature and the precipitated solid was filtered and dried to yield the title compound (weights about 4.3 g, mp (D8C) 114.93 °C).
IR (KBr) cni l : 3413.9, 2934.8, 1663.6, 1571.6, 15457, 1511.8, 1449.0, 1405.5, 1323.2, 1241.8, 1179.3, 1112.1, 1046.5, 956.0,898.9, 853.9, 782.5, 10 736.6, 698.9, 644.7, 557.8.
p- ~: 4.42, 7.58, 7.84, 7.98, 11.64, 11.96, 13.62, 15.76, 16.14, 16.36, 16.54, 17.84, 19.32, 19.46 (20).
Example 50 15 (-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid t-butyl amine salt O
Ph I N~ ~ I ~ ~ NH3 -IN ~ H OC2H5 CH3--~-CH3 CHg O
A ' mixture of (-) 2-ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid (2.0 g) and isopropanol.
20 (15 ml) was heated to reflux to get the clear solution. t-Butylamine (0.35 g) was added slowly dropwise and continued reflux for 2-3 hr. Then the reaction mass was cooled to room temperature and continued stirring for further 2 h.
Then slowly reaction mass cooled to 15 °C, continued stirring for overnight.
Filtered the compound at 10-15 °C, washed with isopropanol (5 ml) dried 25 under high vacuum at 50-60 °C over a period of 8-10 hr to yield the title compound (weights 'about 2.0 g).

DSC: 90.89-105.46 (Endo), 118.30 (Exo), 158.37 (Endo) p-XRD: 4.98, 6.84, 8.52, 10.14, 13.34, 14.64, 15.76, 17.32, 18.16, 19.54, 20.62, 22.20, 23.10, 24.76, 25.60, 27.36, 31.54, 32.46 Cm 1.
IR: 3428, 2977, 1676, 1545, 1512, 1470, 1448, 1402, 1319 1238, 1113, 1047, 900, 854, 781, 699Cm 1.
The compounds of the present invention lowered random blood sugar level, triglyceride, total cholesterol, LDL, VLDL and increased HDL. This was demonstrated by ih vitro as well as ih vivo animal experiments.
Demonstration of Efficacy of Compounds A) Iya vaty~~
a) Determination of hPPARa, activity Ligaiid binding domain of hPPARoc was fused to DNA binding domain of Yeast transcription factor GAL4 in eucaryotic expression vector. Using superfect (Qiagen, Germany) as transfecting reagent HEK-293 cells were transfected with this plasmid and a~reporter plasmid harboring the luciferase a gene driven by a GAL4 specific promoter. Compound was added at different concentrations after 42 hrs of transfection and incubated overnight.
Luciferase activity as. a function of compound binding/activation capacity of PPARoc was measured using Packard Luclite kit (Packard, USA) in Top Count (Ivan Sadowski, Brendan Bell, Peter Broag and Melvyn Hollis. Gene. 1992. 118 137 -141; Superfect Transfection Reagent Handbook. February 1997. Qiagen, Germany).
b) Determination of hPPARy activity Ligand binding domain of hPP'ARy1 was fused to DNA binding domain of Yeast transcription factor GAL4 in eucaryotic 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 gene driven by a GAL4 specific promoter. Compound was added at 1 ~M
concentration after 48 hrs of transfection and incubated overnight. Luciferase activity as a function of drug binding/activation capacity of PPARyl was measured using Packard Luclite kit (Packard, ~JSA) in Packard Top Count (Ivan Sadowski, Brendan Bell, Peter Broag and Melvyn Iiollis. Gene. 1992.
118 .: 137 -141; Guide to Eukaryotic Transfections with Cationic Lipid Reagents. Life Technologies, GIBCO BRL, IJSA).
~xannple ConcentrationppARoc PPARy Concentration No.

11 ~ 50 ~M 13.8 1 p,M 27.0 16 S 0 ~M 3.4 1 ~M 13.5 20 50 ~M 3.5 1 ~M 13.0 23 50 ~M 3.4 1 ~,M 11.5 36 50 pM 3.3 1 p,M 11.4 38 ' SOp.M 3.3e l,uM 12.0 41 50 p.M 3.1 1 ~,M 13.0 44 50 ~,M 2.5 1 ~M 12.0 c) Determination of I~1VIG CmE1 reductase inhibition activity Liver microsome bound reductase is prepared from 2% cholestyramine fed rats at mid-dark cycle. Spectrophotometric assays are carried out in 100 mM I~HaP04, 4 mM DTT, 0.2 mM NADPH, 0.3 mM HMG CoA and 125 ~.g of liver microsomal enzyme. Total reaction mixture voluriie is kept as 1 ml.
Reaction is started by addition of HMG CoA. Reaction mixture is incubated at 37°C for 30 min and decrease in absorbance at 340 nm is recorded.
Reaction mixture without substrate is used as blank (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 Res. 1984, 25: 1450 - 1461). The test compounds will inhibit the HMCp CoA reductase enzyme.
'In vavo a) Efficacy in genetic modeYs 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 zucker fa/fa rats have been developed by the various laboratories for understanding the pathophysiology of disease and testing the efficacy of new antidiabetic compounds (Diabetes, (1983) 32:
830-838 ; Annu. Rep. Sankyo Res. Lab. (1994). 46 : I-57). 'The homozygous animals, C57 BL/KsJ-db/db mice developed by Jackson Laboratory, I_TS, are obese, hyperglycemic, hyperinsulinemic and insulin resistant (J. Clin.
Invest., (1990) 85 : 962-9'67), whereas heterozygous are lean and norinoglycemic. In db/db model, mouse progressively develops insulinopenia with 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 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 I4 weeks age, having body weight range of 35 to 60 grams, bred at Dr. Reddy's Research Foundation (DRF) animal house, were used in the experiment. The mice were provided with standard feed (National Institute of Nutrition (NIN), Iiyderabad, India) and acidified water, ad libitum. 'The anirilals having more than 350 mg / dl blood sugar were used for testing. The number of animals in each group was 4.

Test compounds were suspended on 0.25 % carboxymethyl cellulose and administered to test group at a dose of 0.1 mg to 30 mg / kg through oral gavage daily for 6 days. The control group received vehicle (dose 10 ml / kg).
On 6th day the blood samples were collected one hour after administration of test compounds / vehicle for assessing the biological activity.
The random blood sugar and triglyceride levels were measured ~ by collecting blood (100 ~1) through orbital sinus, using heparinised capillary in tubes containing EDTA which was centrifuged to obtain plasma. The plasma glucose and triglyceride levels were measured spectrometrically, by glucose oxidase and glycerol-3-P04 oxidase/peroxidase enzyme (I~r. Reddy's Lab.
I3iagnostic Division Kits, Hyderabad, India) methods respectively.
The blood sugar and triglycerides lowering activities of the test compound was calculated according to the formula.
No adverse effects were observed for any of the mentioned compounds of invention in the above test.
example Dose (mg / Reduction in Blood Glucose No. kg) )Level (/~) Fxample 0.1 61 The ob/ob mice are obtained at 5 weeks of age from Bomholtgard, Denmark and are used at 8 weeks of age. Zucker falfa fatty rats are obtained from IffaCredo, France at 10 weeks of age and are used at 13 weeks of age.
The animals are maintained under 12 hour light and dark cycle at 25 + 1 °C.
Animals are given standard laboratory chow (N1N, Hyderabad, India) and water, ad libitum (Fujiwara, T., Yoshioka, S., Yoshioka, T., ZJshiyama, I and Horikoshi, H. Characterization of new oral antidiabetic agent CS-045. Studies in KK and ob/ob mice and Zucker fatty rats. Diabetes. 1988. 37 : 1549 -1558).

The test compounds will be administered at 0.1 to 30 mg/kg/day dose for 9 days. The control animals receives the vehicle (0.25%
carboxymethylcellulose, dose 10 ml/kg) through oral gavage.
The blood samples can be collected in fed state 1 hour after drug 5 administration on 0 and 9 day of treatment. The blood can be collected from the retro-orbital sinus through heparinised capillary in EDTA containing tubes.
After centrifugation, plasma sample will be separated for triglyceride, glucose, free fatty acid, total cholesterol and insulin estimations. Measurement of plasma triglyceride, glucose, total cholesterol can be done using commercial 10 kits (Dr. Reddy's Laboratory, Diagnostic Division, India). The plasma free fatty acid will be measured using a commercial kit from Boehringer Mannheim, Germany. The plasma insulin can be measured using a RIA kit (BARC, India). The reduction of various parameters examined will be calculated according to the formula given below.
15 In ob/ob mice oral glucose tolerance test is performed after 9 days treatment. Mice are fasted for 5 hrs and challenged with 3 ,gm/kg of glucose orally. The blood samples are collected at 0, 15, 30, 60 and 120 min for estimation of plasma glucose levels.
b) Plasma tri~lyceride and Cholesterol lowerin~activity in 20 hypercholesterolemic rat models Male Sprague Dawley rats (NIN stock) are bred in DRF animal house.
Animals are maintaW ed under 12 hour light and dark cycle at 25 ~
1°C. Rats of 180 - 200 gram body weight range were used for the ea~periment. Animals are made hypercholesterolemic by feeding 2% cholesterol and 1 % sodium 25 cholate mixed with standard laboratory chow [National Institute of Nutrition (NIN), Hyderabad, India] for 6 days. Throughout the experimental period ,the animals are maintained on the same diet (Petit, D., Bonnefis, M. T., Rey, C
and Infante, R. Effects of ciprofibrate on liver lipids and lipoprotein synthesis a in norino- and hyperlipidemic rats. Atherosclerosis. 1988. 74 : 21S - 225).

The test compounds can be administered orally at a dose 0.1 to 30 mg/kg/day for 3 days. Control group is treated with vehicle alone (0.25 Carboxymethylcellulose; dose 10 ml/kg).
The blood samples can be collected in fed state 1 hour after drug administration on 0 and 3 day of compound treatment: The blood can be collected from the retro-orbital sinus through heparinised capillary in EDTA
containing tubes. After centrifugation, plasma sample will be separated for total cholesterol, HDL and triglyceride estimations. Measurement of plasma triglyceride, total cholesterol and HDL are done using cbmmercial kits (Dr.
Reddy's Laboratory, Diagnostic Division, India). LDL and VLI~L cholesterol can be calculated from the data obtained for total cholesterol, HDL and triglyceride. The reduction of various parameters examined are calculated according to the formula given below.
c) Plasma tri~lyceride and total cholesterol lowering activity in Swiss albino mice and Guinea pigs Male Swiss albino mice (SAM) and male Guinea pigs were obtained from NAT and housed in DRF animal house. All these animals were maintained under 12 hour light and dark cycle at 25 ~ 1 °C. Animals were given standard laboratory chow (NIN, Hyderabad, India) and water, ad libitum. SAM of 20 - 25 g body weight range and Guinea pigs of 500 - 700 g body weight range were used (Oliver, P., Plancke, M. O., Marzin, D., Clayey, V., Sauzieres, J and Fruchart, J. C. Effects of fenofibra~e, gemfibrozil and nicotinic acid on plasma lipoprotein levels in normal and hyperlipidemic mice.
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 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% Carboxymethylcellulose;
dose 5 ml/kg).
The blood samples were collected in fed state 1 hour after drug administration on 0 and 6 day of treatment. The blood was collected from the retro-orbital sinus through heparinised capillary in ED'I'A containing tubes.
After centrifugation, plasma sample was separated for triglyceride and total cholesterol (Wieland; ~. Methods of Enzymatic analysis. Bergermeyer, H. O., Ed., 1963. 211 - 214; Trinder, P. Ann. Olin. Biochem. 1969. 6 : 24 - 27).
Measurement of plasma triglyceride, total cholesterol, and HDL were done using commercial kits (Dr. Reddy's Diagnostic Division, Hyderabad, India).
Example Dose (mg / kg) Triglyceride Lowering No. (%) 1 3 ' 87 11 0.3 58 12 0.3 37 d) Body weight reducing effect in cholesterol fed hamsters Male Syrian Hamsters are procured from NIN, Hyderabad, India.
Animals are housed at DRF animal house under 12 hour light and dark cycle at 25 ~ 1°C with free access to food and water. Animals are maintained with 1 % cholesterol containing standard laboratory chow (N1N) from the day of treatment.
The test compounds can be administered orally at 1 to 30 mg/kg/d~ay dose for 15 days. Control group animals are treated with vehicle (Mill Q
water, dose 10 ml/kg/day). Body weights are measured on every 3rd day.

Formulae for calculation 1. Percent reduction in Blood sugar / triglycerides / total cholesterol were calculated according to the formula TT / OT
Percent reduction (%) = 1 - X 100 TC / OC
OC = Zero day control group value OT = Zero day treated group value TC = Test day control group value TT = Test day treated group value 2. LDL and VLDL cholesterol levels were calculated according to the formula Triglyceride LDL cholesterol in mg/dl = - [ Total cholesterol - HDL cholesterol - ] mg/dl VLDL cholesterol in mg/dl = [Total . cholesterol - HDL cholesterol - LDL
cholesterol] mg/dl.
Single dose oral pharmacokinetic studies Male VVistar rats (220 - 250 gm) were used in the experiments. The animals were maintained under standard laboratory conditions and had free access to feed and water ad libitum. Before experimentation animals were fasted overnight (~15 h) during which they had free access to water ad libitum.
An amount equivalent to 30 mg of drug was weighed accurately and transferred into a clean mortar and triturated to obtain a fine powder. To this 0.5 ml of 0.25% sodium carboxy methyl cellulose (sodium CMC) was added to obtain a paste. To the obtained paste remaining 2.5 ml of sodium CMC was added to make up the volume to 3 ml. Based on the animal weight appropriate volume (body weight x 3) of the prepared suspension was administered through oral gavage.
After dosing, at designated time points (0.5, 1, 2, 3, 5, 8, 12 and 24 h) 200 ~Zl of blood was collected from retro orbital plexus into 0.5 ml eppendorff tubes containing EDTA (10 g.1 of 200 mg/ml solution in Milli Q water). Blood was centrifuged at 12,800 rpm for 5 min and obtained plasma and stored at -20 °C till further analysis.
1001 plasma was transferred into a clean and dry centrifuge tube. To this internal standard (10 ~l of 100 ~g/ml) was added and extracted With 2 ml of extraction recovery solvent. The contents were vortexed for 2 min, followed by centrifugation for 10 min at 2800 rpm. Clear organic layer (2 x 0.75 ml) was separated and dried under nitrogen gas at 50 °C: The residue was reconstituted with 150 w1 of mobile phase and vortexed for 20 sec, from this 50 ~.1 was injected onto HPLC column.
Pharmacokinetic parameters were calculated by non-compartmental model analysis. The peak plasma concentration (CmaX) and the corresponding time (TmaX) were directly obtained from the raw data. The area under the plasma concentration versus time curve up to the last quantifiable time point, AUC~o_t~ was obtained by the linear and log-linear trapezoidal summation. The AUC~o_t~ extrapolated to infinity (i.e., AUC ~0_~1) by adding the quotient of Clast~ela Where Coast represents the last measurable time concentration and I~el represents the apparent terminal rate constant. I~~ was calculated by the linear regression of the log-transformed concentrations of the drug in the terminal phase. The half life of the terminal elimination phase was obtained using the relationship tyz = 0.693/ I~~.
Example AUC ~o_~) AUC ~o_t~Cn,ax Tn,ax W (h') $n2 (h) (h) No. (pg.hrlml (~g.hr/ml(~,g/ml) 4 38.36 6.7640.55 38.67 0.50 0.31 1.97 + +

6.93 10.76 0.00 0.15 0.46 7 51.43 16.2451.65 40.25 0.90 0.38 1.91 + +

16.34 16.93 0.22 0.09 0.41 74.07 21.2675.89 54.21 0.50 0.34 2.16 21.03 19.66 0.00 0.08 0.58 31 65.93 15.5464.70 19.15 2.75 0.34 2.24 +

15.82 5.01 1.50 Ø12 0.87 40 78.55 19.4977.80 34.19 0.75 0.60 1.20 19.27 10.03 0.29 0.13 0.25 ~

45 , 101.29 99.33 24.22 2.38 0.42 1.72 14.76 15.42 9.94 2.06 0.09 0.38 .

47 83.28 10.4582.25 39.54 0.50 0.34 2.07 +

10.61 10.43 0.00 0.04 0.22 46 62.91 8.7861.25 17.69 1.33 0.32 2.19 +

8.86 5.74 ' 0.75 0.03 0.20 48 92.57 27.28'90.12 50.44 0.50 0.29 2.18 28.59 11.12 0.00 0.11 0.61

Claims (38)

Claims

1. Pharmaceutically acceptable salts of the general formula (I) their derivatives, their analogs, their tautomeric forms, their stereoisomers, .
their solvates, their polymorphs, wherein R1 represents hydrogen, alkyl or aryl group; M represents a counter ion or a moiety which forms a pharmaceutically acceptable salt; p is an integer ranging from 1 to 2; A represents a cyclic structure given below:

wherein R2 and R3 may be same or different and independently represent hydrogen, halogen, hydroxy, nitro, cyano, alkyl or alkoxy group; R4 represents hydrogen, halogen, hydroxy, nitro, cyano, azido, formyl or unsubstituted or substituted groups selected from alkyl, cycloalkyl, alkoxy, aryl, heterocyclyl, heteroaryl, amino, monoalkylamino, dialkylamino or alkoxyalkyl groups.

2. A compound according to claim 1 wherein M represents a counter ion or a moiety selected from sodium, Mg, calcium, potassium, Li, glucamine, N-methyl glucamine, N-octyl glucamine, dicyclohexylamine, t-butyl amine, methyl benzylamine, tris(hydroxymethyl)amino methane (tromethamine), phenyl glycinol, lysine, arginine, metformin, aminoguanidine, aminoguanidine hydrogen carbonate, imidazole, piperazine, dimethyl piperazine, pyrrolidine, benzylamine, phenyl glycine methyl ester, phenylalanine benzyl ester or morpholine.

3. A process for the preparation of pharmaceutically acceptable salts of the general formula (I) their derivatives, their analogs, their tautomeric forms, their stereoisomers which comprises: reacting compound of the formula (III) wherein R1 represents hydrogen, alkyl or aryl group; A represents a cyclic structure given below:

where R2 and R3 may be same or different and represent hydrogen, halogen, hydroxy, nitro, cyano, alkyl, alkoxy group; R4 represents hydrogen, halogen, hydroxy, nitro, cyano, azido, formyl or unsubstituted or substituted groups selected from alkyl, cycloalkyl, alkoxy, aryl, heterocyclyl, heteroaryl, amino, monoalkylamino, dialkylamino or alkoxyalkyl group, with a stoichiometric amount of a base in the presence of a solvent.

4. The process as claimed in claim 3, wherein the base used is selected from sodium hydroxide, sodium methoxide, potassium hydroxide, calcium hydroxide, lithium hydroxide, magnesium hydroxide, glucamine, N-methylglucamine, N-octylglucamine, dicyclohexylamine, t-butylamine, methyl benzylamine, tris(hydroxymethyl)aminomethane, phenyl glycinol, lysine, arginine, metformin, aminoguanidine, aminoguanidine hydrogen carbonate, imidazole, piperazine, dimethyl piperazirie, pyrrolidine, benzylamine, phenyl glycine methyl ester, phenylalanine benzyl ester or morpholine.

5. The process as claimed in claims 3 and 4, wherein the reaction is effected in the presence of solvent selected from alcohols, ketones, ethers, DMF, DMSO, xylene, toluene, ethyl acetate or their mixture.

6. The process as claimed in claims 3 to 5, wherein the reaction is carried out at a temperature in the range of -10 °C to the boiling point of the solvent employed for a period in the range of 10 minutes to 30 hours.

7. A pharmaceutically acceptable salt according to claim 1, which is selected from:
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-y1)ethoxy]phenyl]-2-ethoxypropanoic acid phenyl glycinol salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid phenyl glycinol salt;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid phenyl glycinol salt;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid methyl benzylamine salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid methyl benzylamine salt;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid methyl benzylamine salt;

(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-y1)ethoxy]phenyl]-2-ethoxypropanoic acid dicyclohexylamine salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4=dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid dicyclohexylamine salt;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid dicyclohexylamine salt;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid lysine salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid lysine salt;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid lysine salt;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid tris (hydroxymethyl)amino methane salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid tris (hydroxymethyl)amino methane salt;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid tris (hydroxymethyl)amino methane salt;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid N-octyl glucamine salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxpropanoic acid N-octyl glucamine salt;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid N-octyl glucamine salt;

(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid N-methyl glucamine salt;

(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin=3-yl)ethoxy]phenyl]-2,-ethoxypropanoic acid N-methyl glucamine salt;

(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid N-methyl glucamine salt;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid amino guanidine hydrogen carbonate salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid amino guanidine hydrogen carbonate salt;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid amino guanidine hydrogen carbonate salt ;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid lithium salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid lithium salt;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid lithium salt;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid arginine salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid arginine salt ;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid arginine salt ;

(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid metformin salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid metformin salt;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid metformin salt;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid imidazole salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid imidazole salt;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid imidazole salt;
(~) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt;
(+) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt;
(-) 3-[4-[2-(2-Ethyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt;
(~) 3-[4-[2-(2-Morpholinyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt;
(+) 3-[4-[2-(2-Morpholinyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt;
(-) 3-[4-[2-(2-Morpholinyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt;

(~) 3-[4-[2-(2-Piperidinyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt;
(+) 3-[4-[2-(2-Piperidinyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt;
(-) 3-[4-[2-(2-Piperidinyl-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt;
(~) 3-[4-[2-(2-Azido-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt;
(+) 3-[4-[2-(2-Azido-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt;
(-) 3-[4-[2-(2-Azido-4-oxo-3,4-dihydroquinazolin-3-yl)ethoxy]phenyl]-2-ethoxypropanoic acid magnesium salt;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid magnesium salt;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid magnesium salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2,-ethoxypropionic acid magnesium salt;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid magnesium salt;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid magnesium salt;
(-) 3-[4-[~-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid magnesium salt;

(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid potassium salt;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid potassium salt;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid potassium salt;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid potassium salt;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid potassium salt;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid potassium salt;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid calcium salt;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid calcium salt;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid calcium salt;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6a7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid calcium salt;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid calcium salt;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid calcium salt;

(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lithium salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lithium salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lithium salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lithium salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lithium salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lithium salt ;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid sodium salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid sodium salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid sodium salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid sodium salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid sodium salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid sodium salt ;

(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid arginine salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid arginine salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid arginine salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid arginine salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid arginine salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid arginine salt ;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid methyl benzylamine salt;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid methyl benzylamine salt; .
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid methyl benzylamine salt;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid methyl benzylamine salt;

(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid methyl benzylamine salt;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid methyl benzylamine salt;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid S-(+)-phenylglycinol salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid S-(+)-phenylglycinol salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid S-(+)-phenylglycinol salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid S-(+)-phenylglycinol salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid S-(+)-phenylglycinol salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid S-(+)-phenylglycinol salt ;

(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aminoguanidine salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aminoguanidine salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aminoguanidine salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aminoguanidine salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aminoguanidine salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid aminoguanidine salt ;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid tromethamine salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid tromethamine salt;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid tromethamine salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid tromethamine salt ;

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

(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid dicyclohexylamine salt;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid dicyclohexylamine salt;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid dicyclohexylamine salt;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid dicyclohexylamine salt;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid dicyclohexylamine salt;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid dicyclohexylamine salt;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-octylglucamine salt;

(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-octylglucamine salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-octylglucamine salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-octylglucamine salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-octylglucamine salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-octylglucamine salt ;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-methylglucamine salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-methylglucamine salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-methylglucamine salt ;

(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-methylglucamine salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-methylglucamine salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid N-methylglucamine salt ;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid metformin salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid metformin salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid metformin salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid metformin salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid metformin salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid metformin salt ;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lysine salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lysine salt ;

(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lysine salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lysine salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lysine salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid lysine salt ;
(~) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid t-butylamine salt ;
(+) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid t-butylamine salt ;
(-) 3-[4-[2-(1-Methyl-5-ethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid t-butylamine salt ;
(~) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid t-butylamine salt ;
(+) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid t-butylamine salt ;
(-) 3-[4-[2-(1,5-Dimethyl-7-oxo-3-propyl-6,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-6-yl)ethoxy]phenyl]-2-ethoxypropionic acid t-butylamine salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid potassium salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid potassium salt ;

(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid potassium salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid sodium salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid sodium salt ;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid sodium salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid L-lysine salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid L-lysine salt ;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid L-lysine salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid t-butylamine salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid t-butylamine salt ;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid t-butylamine salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid N-methyl glucamine salt;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid N-methyl glucamine salt;

(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid N-methyl glucamine salt;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid N-octyl glucamine salt;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid N-octyl glucamine salt;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid N-octyl glucamine salt;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid tris (hydroxymethyl)amino methane salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid tris (hydroxymethyl)amino methane salt ;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid tris (hydroxymethyl)amino methane salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid lithium salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid lithium salt ;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid lithium salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid calcium salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid calcium salt ;

(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid calcium salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid L-arginine salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid L-arginine salt ;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid L-arginine salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid metformin salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid metformin salt ;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid metformin salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid dicyclohexylamine salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid dicyclohexylamine salt ;
(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid dicyclohexylamine salt ;
(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid aminoguanidine salt ;
(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid aminoguanidine salt ;

(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid aminoguanidine salt;

(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid magnesium salt;

(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid magnesium salt;

(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid magnesium salt;

(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid phenyl glycinol salt;

(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid phenyl glycinol salt;

(-) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid phenyl glycinol salt;

(~) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid methyl benzylamine salt;

(+) 2-Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid methyl benzylamine salt;

(-) 2- Ethoxy-3-[4-[2-[2-ethyl-6-oxo-4-phenyl-1,6-dihydropyrimidin-1-yl]ethoxy]phenyl]propanoic acid methyl benzylamine salt;

8. A pharmaceutical composition, which comprises a compound of formula (I) as defined in claim 1 or a compound as claimed in claim 7 and a pharmaceutically acceptable carrier, diluent, excipient or solvate.

9. A pharmaceutical composition as claimed in claim 8 in the form of a tablet, capsule, powder, syrup, solution or suspension.

10. A composition which comprises a compound of formula (I) as defined in claim 1 or a compound as claimed in claim 7 and an HMG CoA reductase inhibitor, fibrate, nicotinic acid, cholestyramine, cholestipol, probucol or a mixture thereof and a pharmaceutically acceptable carrier, diluent, excipient or solvate.

11. A pharmaceutical composition as claimed in claims 8 and 9 for the treatment of type II diabetes, unpaired glucose intolerance, leptin resistance, atherosclerosis, hyperlipidemia, disorders related to Syndrome X such as hypertension, obesity, insulin resistance, coronary artery disease and other cardiovascular disorders, renal diseases including glomerulonephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis, nephropathy; retinopathy, disorders related to endothelial cell activation, psoriasis, polycystic ovarian syndrome (PCOS), dementia, diabetic complications, eating disorders, osteoporosis, inflammatory bowel diseases, myotonic dystrophy, pancreatitis, retinopathy, arteriosclerosis, xanthoma ,or cancer.

12. A method of treating hyperlipidemia, 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 a compound of formula (I) as defined in claim 1 or a compound as claimed in claim 7 or a pharmaceutical composition according to claim 8 or 9 to a patient in need thereof.

13. A method according to claim 12, wherein the disease is type II diabetes, impaired glucose tolerance, disorders related to Syndrome X such as hypertension, obesity, insulin resistance, atherosclerosis, coronary artery disease and other cardiovascular disorders; renal diseases including glomerulonephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis, nephropathy; retinopathy, disorders to related endothelial cell activation, psoriasis, polycystic ovarian syndrome (PCOS), dementia, diabetic complications, inflammatory bowel diseases, myotonic dystrophy, pancreatitis, arteriosclerosis, xanthoma, eating disorders, cancer or osteoporosis or as inflammatory agents.

14. A method according to claim 12, for the treatment of disorders related to Syndrome X, which comprises administering an agonist of PPAR.alpha. and/or PPAR.gamma. of formula (I) as claimed in claim 1 or a compound as claimed in claim 7 or a pharmaceutical composition according to claim 8 or 9 to a patient in need thereof.

15. A method of reducing total cholesterol, body weight, blood plasma glucose, triglycerides, LDL, VLDL or free fatty acids or increasing HDL in the plasma comprising administering a compound of formula (I), as defined in claim 1 or a compound as claimed in claim 7 or a pharmaceutical composition according to claim 8 or 9 to a patient in need thereof.

16. A method of 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 to a patient in need thereof an effective amount of a compound of formula (I) as defined in claim 1 or a compound as claimed in claim 7 or a pharmaceutical composition according to claim 8 or 9 in combination/concomittant with a HMG CoA reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol or their combination within such a period so as to act synergistically.

17. A method according to claim 16, wherein the disease is type II diabetes, impaired glucose tolerance, disorders related to Syndrome X such as hypertension, obesity, insulin resistance, atherosclerosis, coronary artery disease and other cardiovascular disorders; renal diseases including glomerulonephritis, glomerulosclerosis, nephrotic syndrome, hypertensive nephrosclerosis, nephropathy; retinopathy, disorders to related endothelial cell activation, psoriasis, polycystic ovarian syndrome (PCOS), dementia, diabetic complications, inflammatory bowel diseases, myotonic dystrophy, pancreatitis, arteriosclerosis, xanthoma, eating disorders, cancer or osteoporosis or as inflammatory agents.

18. A method according to claim 16, for the treatment of disorders related to Syndrome X, which comprises administering to a patient in need thereof an agonist of PPAR.alpha. and/or PPAR.gamma. of formula (I) as claimed in claim 1 or a compound as claimed in claim 7 or a pharmaceutical composition according to claim 8 or 9 and a HMG CoA reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol or their combination within such a period as to act synergistically.

19. A method of reducing plasma glucose, triglycerides, total cholesterol, LDL, VLDL or free fatty acids or increasing HDL in the plasma, which comprises administering a compound of formula (I) claimed in claim 1 or a compound as claimed in claim 7 or a pharmaceutical composition according to claim 8 or 9, in combination/concomittant with a HMG CoA reductase inhibitor, fibrates, nicotinic acid, cholestyramine, colestipol or probucol which may be administered together or within such a period as to act synergistically together to a patient in need thereof.

20. Use of a compound of formula (I) as defined in claim 1 or a compound as claimed in claim 7 or a pharmaceutical composition according to claim 8 or 9 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.

21. Use of a compound according to claim 20, 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.

22. Use of a compound of formula (I) as defined in claim 1 or a compound as claimed in claim 7 or a pharmaceutical composition according to claim 8 or 9 for reducing plasma glucose, triglycerides, total cholesterol, LDL, VLDL or free fatty acids or increasing HDL in the plasma.

23. Use of a compound of formula (I) as defined in claim 1 or a compound as claimed in claim 7 or a pharmaceutical composition according to claim 8 or 9 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.

24. Use of a compound according to claim 23, 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.

25. Use of a compound of formula (I) as defined in claim 1 or a compound as claimed in claim 7 or a pharmaceutical composition according to claim 8 or 9 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.

26. Use of a compound of formula (I) as defined in claim 1 or a compound as claimed in claim 7 or a pharmaceutical composition according to claim 8 or 9 for preparing a medicament 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.

27. Use of a compound according to claim 26, 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.

28. Use of a compound of formula (I) as defined in claim 1 or a compound as claimed in claim 7 or a pharmaceutical composition according to claim 8 or 9 for preparing a medicament for reducing plasma glucose, triglycerides, total cholesterol, LDL, VLDL or free fatty acids or increasing HILL in the plasma.

29. Use of a compound of formula (I) as defined in claim 1 or a compound as claimed in claim 7 or a pharmaceutical composition according to claim 8 or 9 for preparing a medicament in combination/concomittant with HMG CoA
reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol 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.

30. Use of a compound according to claim 29, 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.

31. Use of a compound of formula (I) as defined in claim 1 or a compound as claimed in claim 7 or a pharmaceutical composition according to claim 8 or 9 for preparing a medicament 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.

32. 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 7 or a pharmaceutical composition according to claim 8 or 9.

33. A medicine according to claim 32, 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.

34. 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 7 or a pharmaceutical composition according to claim 8 or 9.

35. 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 7 or a pharmaceutical composition according to claim 8 or 9 and HMG CoA reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol.

36. A medicine according to claim 35, 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.

37. 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 7 or a pharmaceutical composition according to claim 8 or 9 and HMG CoA reductase inhibitors, fibrates, nicotinic acid, cholestyramine, colestipol or probucol.

38. The process as claimed in claim 5, wherein the alcohol is selected from a group consisting of ethanol, methanol, isopropanol or butanol; ketone is selected from a group consisting of acetone, diethyl ketone, methyl ethyl ketone or their mixtures; ether is selected from a group consisting of diethyl ether, ether, tetrahydrofuran, dioxane, dibutyl ether.