INTRODUCTION:

The chemical reactivity of the pyrazole molecule can be explained by the effect of individual atoms. The N-atom at position 2 with two electrons is basic and therefore reacts with electrophiles. The N-atom at position 1 is unreactive, but loses its proton in the presence of base. The combined two N-atoms reduce the charge density at C3 and C5, making C4 available for electrophilic attack.

Deprotonation at C3 can occur in the presence of strong base, leading to ring opening. Protonation of pyrazoles leads to pyrazolium cations that are less likely to undergo electrophilic attackat C4, but attack at C3 is facilitated. The pyrazole anion is much less reactive toward nucleophiles, but the reactivity to electrophiles is increased. Pyrazoles have been proved to possess analgesic, anti-inflammatory, anti pyretic, ant diabetic, antibacterial, antifungal, ant tubercular, anti parasitic, insecticidal, cytotoxic activities^1-15.

More specifically 1-phenylpyrazole derivatives are known to have a broad spectrum of biological activities. For example, Sulfaphenazole is a potent antibacterial drug. Nonsteriodal anti inflammatory drugs such as Lonazolac are (1, 3-diphenyl-1H-pyrazol-4-yl) acetic acid derivatives. The widely prescribed COX-2 inhibitor Celecoxib carries a triflouromethyl substituent at the C-3 of the pyrazole nucleus and a partial sulfonamide structure at the N-phenyl ring. 1, 3-diphenylpyrazoles containing heterocyclic moieties such as pyrimidine, oxadiazole and triazole at the C-4 have been tested for their antimicrobial, antifungal and antiviral activities^16-19. 4-alkyl-1, 2, 5-tri (4-hydroxyphenyl) pyrazoles have been studied as estrogen receptor selective agonists.

Many methods have been described in the literature for the synthesis of substituted pyrazoles. The most common approach is cyclocondensation of α, β-unsaturated carbonyl compounds with hydrazine or arylhydrazines and subsequent dehydrogenation. In order to develop an efficient synthetic approach to the various 3 and 5 substituted-1H-pyrazoles we chose to ceric ammonium nitrate as dehydrogenating agent. Although this method has found many applications in synthesizing novel pyrazoles, there is still a great deal of work remaining to enable the development of efficient protocols for structurally different compounds and to make these reactions more practical by using inexpensive and easily available starting materials.

MATERIALS AND METHODS:

All the required chemicals used were obtained from Aldrich and Sd-fine chemicals. Pre coated TLC plates (0.25mm silica gel) were obtained from E. Merck. All the synthesized compounds were purified by recrystallization. Melting points were determined on Fisher Johns melting point apparatus. All the H1- NMR spectra were recorded on the spectra were recorded on sophisticated multinuclear FT-NMR spectrometer model Avance-II (Bruker). Mass spectra of the compounds were recorded on Mass spectrometer model Aligent 1100 series.

Scheme: 1

Preparation of glucoacetate compound (2):

Glucose was taken in 100ml round bottom flask and acetic anhydride was added as solvent. 3-4 drops of concentrated sulphuric acid was added to the above solution. The resultant mixture was heated up to 100°C for 2 hours. Progress of reaction was monitored by TLC. The solvent (acetic acid) was removed through down ward distillation.

Preparation of 2-(acetoxymethyl)-6-bromotetrahydro-2H-pyran-3, 4, 5-triyl triacetate(3):

Compound –A was taken in 3 necked round bottom flask at 0⁰C, then passing the hydrobromic acid (HBr) gas.Hydrobromic acid (HBr) gas must be passed for 30 min under cool condition with stirring then keep the resultant mixture infridgeovernight. Then the mixture should heat for 2-3 hours at 600C (for liberation of HBr gas). Then the solvent was removed under 5mm reduced pressures. The residue was dissolved in diisopropylether (DIP) and heated up to boiling the solvent, then filtered the filtrate was slowly get into room temperature. Obtained white solid washed with cool diisopropylether (DIP), the compound obtained was used for next further reactions. Purity of the compound was established by a single spot in TLC and further confirmation was done by IR, H1NMR and mass spectra.

Scheme: 2

Preparation of 4-alkoxy Benzaldehyde (5a-5c):

K2CO3 (50.9g, 0.368mol) was added to the 4-hydroxy benzaldehyde (15g, 0.122mol) solution in acetone as solvent was taken in round bottom flask. The mixture was refluxed for some time then added methyl iodide (34.9g, 0.245 mol), and then the resultant mixture was refluxed for 1 hour. Progress of reaction was moitored by TLC. The reaction mixture was filtered on the celite (for removal of inorganic salts), washed with ethyl acetate. The ethyl acetate layer was further washed with sodium thiosulphate solution, water and brine solution and then dried over anhydrous sodium sulphate. Finally the ethyl acetate layer was evaporated and the 4-alkoxy benzaldehyde obtained was used for next reaction without purification.Purity of the compound was established by a single spot in TLC and further confirmation was done by H1NMR and mass spectra.

Preparation of N-oxide (6a-6c):

Methyl ethyl ketone (5g, 0.069 mol),was taken in round bottom flask and acetic acid was added as solvent and stirred for 10 minutes at room temperature then this mixture was cooled to 0°C. Sodium nitrate (7.18g, 0.104mol) was dissolved in minimum amount of water and added to the above solution drop wisely and stirred 1 hour at 0°C, and then the mixture was leave a room temperature overnight. Acetic acid was added and cooled to 0°C and then added anisaldehyde (10.3g, 0.076mol) to the mixture drop wisely. Then hydrochloric acid gas passes for 2 hours at -5 to -10°C and then leave at room temperature overnight with stirring. Progress of reaction was monitored by TLC. The resultant mixture was extracted with methyl tertiary butyl ether (MTBE) form a solid (salt), filtered and dissolved in ethyl acetate. The ethyl acetate layer was further washed with sodium bicarbonate solution and brine solution and then dried over anhydrous sodium sulphate. Finally the ethyl acetate layer was evaporated and the white crystalline solid obtained was used for next reaction. Purity of the compound was established by a single spot in TLC and further confirmation was done by IR, H1NMR and mass spectra.

Preparation of 4-(chloromethyl)-2-(4-methoxyphenyl)-5-methyloxazole from N-oxide (7a-7c):

Compound-A (10g, 0.046mol) was taken in dry 2 necked round bottom flask and chloroform was added as solvent it was stirred for 10 minutes at room temperature, then the mixture was cooled to 0°C. Then phosphorous oxychloride (8.3ml, 0.137mol) was added to the above solution drop wisely, and then the mixture was refluxed overnight. Progress of reaction was monitored by TLC. Theresultant mixture was quenched with cold water and sodium bicarbonate solution. The solvent was removed over rotatory evaporator and the solid compound in the water was dissolved in ethyl acetate. The ethyl acetate layer was further washed with water and brine solution and then dried over anhydrous sodium sulphate. The ethyl acetate layer was evaporated and the white amorphous compound obtained was used for next reaction. Purity of the compound was established by a single spot in TLC and further confirmation was done by H1NMR and mass spectra.

Preparation of 4-(iodomethyl)-2-(4-methoxyphenyl)-5-methyloxazole(8a-8c):

Sodium iodide (8.86g, 0.059mol) was added to the compound-A (7g, 0.029mol) solution in acetone was taken in round bottom flask, then the mixture was stirred at 60°C for 3 hours. Progress of reaction was monitored by TLC. The solvent was removed over rotatory evaporator and the residue was dissolved in ethyl acetate. The ethyl acetate layer was further washed with sodium thiosulphate solution, water and brine solutionand then dried over anhydrous sodium sulphate. The ethyl acetate layer was evaporated and the pale yellowish solid compound obtained was used for next reaction. Purity of the compound was established by a single spot in TLC and further confirmation was done by H1NMR and mass spectra.

Preparation of ethyl 2-((2-(4-methoxyphenyl)-5-methyloxazol-4-yl) methyl)-3-oxobutanoate (9a-9c):

Ethylacetoacetate (3.83ml, 0.03mol) was added to the sodium hydride (0.73g, 0.03mol) solution in tetra hydro furan as solvent at -5°C to 0°C. The iodo compound (5g, 0.015mol) was dissolved in minimum amount of tetra hydro furan and added to the above solution and stirred for 3 hours at same temperature. Progress of reaction was monitored by TLC. Theresultant mixture was quenched with water and extracted with ethyl acetate. The ethyl acetate layer was further washed with water and brine solutionand then dried over anhydrous sodium sulphate. The ethyl acetate layer was evaporated and the crude compound thus obtained was purified by column chromatography. Purity of the compound was established by a single spot in TLC and further confirmation was done by H1NMR and mass spectra.

Preparation of 4-((2-(4-methoxyphenyl)-5-methyloxazol-4-yl) methyl)-5-methyl-1H-pyrazol-3-ol (10a-10i):

Alkyl hydrazine (0.67g, 0.009mol) was taken in 100ml round bottom flask at room temperature and ethanol was added as solvent. Triethylamine (1.68ml, 0.012mol) was added to the above solution. Ethyl 2-((2-(4-methoxyphenyl)-5-methyloxazol-4-yl) methyl)-3-oxobutanoate (2g, 0.006mol) was dissolved in ethanol and added to the above solution the resultant mixture was refluxed overnight. Progress of reaction was monitored by TLC. The solvent was removed over rotator y evaporator and the residue was dissolved in ethyl acetate and then acidified with 10% HCl solution. The aqueous layer was discarded and the ethyl acetate layer was further washed with brine and then dried over anhydrous sodium sulphate. The ethyl acetate was evaporated and the crude compound thus obtained was purified by column chromatography.Purity of the compound was established by a single spot in TLC and further confirmation was done by H1NMR and mass spectra.

Scheme: 3

Preparation of 2-(acetoxymethyl)-6-(4((2-(4-methoxyphenyl)-5-methyloxazol-4-yl) methyl)-5-methyl-1H-pyrazol-3-yloxy) tetrahydro-2H-pyran-3, 4, 5-triyl triacetate (11a-11i):

4-((2-(4-methoxyphenyl)-5-methyloxazol-4-yl)methyl)-5-methyl-1H-pyrazol-3-ol (0.6g,0.002mol) was taken in a 100ml round bottom flask and dimethylformamide was added as a solvent. Potassium carbonate (0.83g, 0.006mol) was added to the above solution and stirred for 10 min.Bromoglucose (1.6g, 0.004mol) was dissolved in dimethylformamide and added to the above solution and stirred for 5hrs at room temperature. Progress of reaction was monitored by TLC. Added some water to the above solution , the reaction mixture was filtered on the celite (for removal of inorganic salts), washed with ethyl acetate, the organic and aqueous layers were separated, then the aqueous layer extracted 2-3 times with ethyl acetate. The ethyl acetate layerwas washed with water 3-4 times. The ethyl acetate layer was thereafter washed with brine solution and then dried over anhydrous sodium sulphate. Finally the ethyl acetate layer was evaporated and the compound obtained was used for next reaction without purification.Purity of the compound was established by a single spot in TLC and further confirmation was done by H1NMR and mass spectra.

Preparation of 2-(hydroxymethyl)-6-(4-((2-(4-methoxyphenyl)-5-methyloxazol-4-yl) methyl)-5-methyl-1H-pyrazol-3-yloxy) tetrahydro-2H-pyran-3, 4, 5-triol(12a-12i).

2-(acetoxymethyl)-6-(4((2-(4-methoxyphenyl)-5-methyloxazol-4-yl)methyl)-5-methyl-1H-pyrazol-3-yloxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate was taken in round bottom flask and methanolic ammonia was added in presence of nitrogen atmosphere and stirred overnight at room temperature. Progress of reaction was monitored by TLC. The solvent was removed over rotator evaporator and the residue was dissolved in heat ethyl acetate and washed with saturated brine solution and then dried over anhydrous sodium sulphate and ethyl acetate was evaporated and the crude compound thus obtained was purified by column chromatography. Purity of the compound was established by a single spot in TLC and further confirmation was done by IR, H1NMR and mass spectra.

RESULTS AND DISCUSSION:

The synthesis and biological evaluation of novel pyrazole based heterocycles attached to sugar moiety lead to creating a new molecular frame work. Nine new compounds were synthesized by reacting ethyl 2-((2-(4-methoxyphenyl)-5-methyloxazol-4-yl) methyl)-3-oxobutanoate derivatives (9a-9c) with different alkyl hydrazines to give various substituted 4-((2-(4-methoxyphenyl)-5-methyloxazol-4-yl) methyl)-5-methyl-1H-pyrazol-3-ol derivatives (10 a-10i) which in turn were reacted with bromoglucose (3)to yield R1, R2 substituted 2-(4-((2-(4-alkoxyphenyl)-5-methyloxazol-4-yl)methyl)-1-alkyl-5-methyl-1H-pyrazol-3-yloxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (12a-12i). The reactions are depicted in figure-1. List of synthesized compounds (12a-12i) and spectral data of R, R1substituted2 (4-((2-(4-alkoxyphenyl)-5-methyloxazol-4-yl)methyl)-1-alkyl-5-methyl-1H-pyrazol-3-yloxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (12a-12i) were shown in Table-1 and Table-2 respectively.

Figure No: 1. Chemical reactions of the sheme-1,2 and 3.

Table-1. List of synthesized compounds (12a-12i):

Comp	R₁	R₂	IUPAC Name	Structure of final compound
12a	-CH₃	-H	(2S,3R,4R,5S,6R)-2-(hydroxymethyl)-6-(4-((2-(4-methoxyphenyl)-5-methyloxazol-4-yl)methyl)-5-methyl-1H-pyrazol-3-yloxy)tetrahydro-2H-pyran-3,4,5-triol
12b	-CH₃	-C₂H₅	(2R,3S,4R,5R,6S)-2-(1-ethyl-4-((2-(4-methoxyphenyl)-5-methyloxazol-4-yl)methyl)-5-methyl-1H-pyrazol-3-yloxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
12c	-CH₃	-C₃H₇	(2S,3R,4R,5S,6R)-2-(hydroxymethyl)-6-(1-isopropyl-4-((2-(4-methoxyphenyl)-5-methyloxazol-4-yl)methyl)-5-methyl-1H-pyrazol-3-yloxy)tetrahydro-2H-pyran-3,4,5-triol
12d	-C₂H₅	-H	(2R,3S,4R,5R,6S)-2-(4-((2-(4-ethoxyphenyl)-5-methyloxazol-4-yl)methyl)-5-methyl-1H-pyrazol-3-yloxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
12e	-C₂H₅	-C₂H₅	(2R,3S,4R,5R,6S)-2-(4-((2-(4-ethoxyphenyl)-5-methyloxazol-4-yl)methyl)-1-ethyl-5-methyl-1H-pyrazol-3-yloxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
12f	-C₂H₅	-C₃H₇	(2R,3S,4R,5R,6S)-2-(4-((2-(4-ethoxyphenyl)-5-methyloxazol-4-yl)methyl)-1-isopropyl-5-methyl-1H-pyrazol-3-yloxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
12g	-C₃H₇	-H	(2S,3R,4R,5S,6R)-2-(hydroxymethyl)-6-(4-((2-(4-isopropoxyphenyl)-5-methyloxazol-4-yl)methyl)-5-methyl-1H-pyrazol-3-yloxy)tetrahydro-2H-pyran-3,4,5-triol
12h	-C₃H₇	-C₂H₅	(2R,3S,4R,5R,6S)-2-(1-ethyl-4-((2-(4-isopropoxyphenyl)-5-methyloxazol-4-yl)methyl)-5-methyl-1H-pyrazol-3-yloxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
12i	-C₃H₇	-C₃H₇	(2S,3R,4R,5S,6R)-2-(hydroxymethyl)-6-(4-((2-(4-isopropoxyphenyl)-5-methyloxazol-4-yl)methyl)-1-isopropyl-5-methyl-1H-pyrazol-3-yloxy)tetrahydro-2H-pyran-3,4,5-triol

Table-2 . Spectral data of R, R1substituted2 (4-((2-(4-alkoxyphenyl)-5-methyloxazol-4-yl)methyl)-1-alkyl-5-methyl-1H-pyrazol-3-yloxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (12a-12i)

comp	R1	R2	Mass spectra (m/z)	1H NMR spectra (DMSO)
12a	-CH3	-H	484 (M+Na)	δ 2.0 (s,3H),δ 2.25(s,3H),δ 3.10-3.17(m,4H),δ 3.4(d,3H), δ 3.5(d,1H), δ 3.7(s,3H), δ4.4-4.5(t,1H), δ4.9(d,1H), δ5.0(d,1H), δ 5.1(d,1H), δ 5.2(d,1H), δ 6.9-7.0(d,2H), δ 7.7(d,2H), δ 11.4(s,1H).
12b	-CH3	-C2H5	512 (M+Na)	δ1.1-1.2(t,3H), δ1.3(t,3H), δ2.0(s,3H), δ2.3(s,3H), δ3.1(d,2H), δ3.2(s,2H), δ3.4-3.5(d,1H), δ3.6(d,1H), δ3.6(t,2H), δ3.9(m,2H), δ4.0(m,2H), δ4.5(t,1H), δ4.9(d,1H), δ5.0(d,1H), δ5.0(d,1H), δ5.1(d,1H), δ5.6-5.7(d,1H), δ6.9-7.0(d,2H), δ7.7-7.8(d,2H).
12c	-CH3	-C3H7	526 (M+Na)	δ 1.21-1.23(t,3H), δ1.26-1.28(d,6H), δ1.75(s,2H), δ2.0(s,3H), δ2.0(s,2H), δ2.2(s,3H), δ3.1(m,4H), δ3.5(m,1H), δ3.6(m,1H), δ3.6(m,1H), δ3.9(q,2H), δ4.5(t,1H), δ4.6((m,1H), δ4.8(d,1H), δ5.0(d,1H), δ5.1(d,1H), δ5.6-5.7(d,1H), δ6.9-7.0(d,2H), δ7.6-7.8(d,2H).
12d	-C2H5	-H	498(M+Na)	δ 1.31-1.35(t,3H), δ 2.1(s,3H), δ 2.2(s,3H), δ3.1(m,4H) δ 3.4(s,2H), δ3.6(s,1H), δ4.0(d,2H), δ4.5(s,1H), δ4.9(s,1H), δ5.0(s,1H), δ5.1(s,1H), δ5.2(s,1H), δ6.9-7.0(d,2H), δ7.7-7.8(d,2H).
12e	-C2H5	-C2H5	526(M+Na)	δ1.1-1.2(t,3H), δ1.3(t,3H), δ2.0(s,3H), δ2.3(s,3H), δ3.1(d,2H), δ3.2(s,2H), δ3.4-3.5(d,1H), δ3.6(d,1H), δ3.6(t,2H), δ3.9(m,2H), δ4.0(m,2H), δ4.5(t,1H), δ4.9(d,1H), δ5.0(d,1H), δ5.0(d,1H), δ5.1(d,1H), δ5.6-5.7(d,1H), δ6.9-7.0(d,2H), δ7.7-7.8(d,2H).
12f	-C2H5	-C3H7	540(M+Na)	δ1.23-1.30(d,6H), δ1.33-1.35(t,3H), δ 2.02(s,3H), δ2.29(s,3H), δ3.17(s,2H), δ3.24-3.25(m,2H), δ3.55(s,1H), δ3.60(s,2H),3.63-3.68(m,2H), δ4.0-4.1(q,2H), δ4.5-4.6(m,1H), δ4.6-4.8(m,1H), δ5.0(d,1H), δ5.1(d,1H), δ5.6(d,1H), δ6.9(d,2H), δ7.7-7.8(d,2H).
12g	-C3H7	-H	512(M+Na)	δ 1.32-1.34(d,6H), δ2.18(s,3H), δ2.31(s,3H), δ3.34(s,2H), δ3.1-3.4(t,2H), δ3.6(s,2H), δ3.6-3.8(m,1H), δ3.8(dd,1H), δ4.62-4.67(m,1H), δ5.0(m,1H), δ6.9(d,2H), δ7.8(d,2H).
12h	-C3H7	-C2H5	540(M+Na)	δ 1.21-1.23(t,3H), δ1.26-1.28(d,6H), δ1.75(s,2H), δ2.0(s,3H), δ2.0(s,2H), δ2.2(s,3H), δ3.1(m,4H), δ3.5(m,1H), δ3.6(m,1H), δ3.6(m,1H), δ3.9(q,2H), δ4.5(t,1H), δ4.6((m,1H), δ4.8(d,1H), δ5.0(d,1H), δ5.1(d,1H), δ5.6-5.7(d,1H), δ6.9-7.0(d,2H), δ7.6-7.8(d,2H).
12i	-C3H7	-C3H7	554(M+Na)	δ 0.9-1.0(d,2H), δ1.2(m,12H), δ1.9(s,3H), δ2.2(s,3H), δ3.1(s,2H), δ3.2(d,2H), δ3.4(m,1H), δ3.5(d,2H), δ3.6(d,1H), δ4.4-4.5(t,1H), δ4.6(m,2H), δ4.8(t,1H), δ5.0(d,1H), δ5.1(d,1H), δ5.6(d,1H), δ6.9(d,2H), δ7.7(d,2H).

Table-3. Anti diabetic data of synthesized compounds

				Urine glucose (mg/BW) at following					Total UGE in 24-h
Treatment	Dose(mg/kg)	R₁	R₂	Time intervals					(mg/BW)
				2hr	4hr	6hr	12hr	24hr
Control	--	--	--	--	--	--	--	--	0
Standard	30	-C₃H₇	-C₃H₇	6.5	18.5	40	90	165	320
12a	100	-CH₃	-H	0.5	3	6	10.5	30	50
12c	100	-CH₃	-C₃H₇	0.4	6	9	19.5	26.1	61
12e	100	-C₂H₅		0.4	5.3	10.6	12	25.7	54
12f	100	-C₂H₅	-C₃H₇	0.8	7.8	15.6	30.6	50.2	105
12g	100	-C₃H₇	-H	0.3	6.9	17.5	25.3	45	95
12h	100	-C₃H₇	-C₂H₅	0.6	8.3	18.5	52.6	70	150
12i	100	-C₃H₇	-C₃H₇	1.8	11.3	33.3	62.4	98.2	207

Anti-diabetic activity:

The anti diabeticactivity of all the nine compounds was determined by Urinary Glucose Excretion (UGE) Method byusing male Sprague-Dawley rats weighing 170-210gm as test animals. Remogliflozin was used as a standard (10mg/kg ) suspended in a 0.5% carboxy methyl cellulose suspension and administered at dose of it. All the compounds were screened for anti diabetic activity at the concentration 90mg/kg by using glucose analyzer (Olympus AU 400). The following table summarizes the effects of vehicle, synthesized compounds and remogliflozin on urine glucose level at various time points during urinary glucose excretion (UGE) test in male Sprague-Dawley rats. All data listed as mean means ±SE. The urine glucose levels of vehicle treated rats, synthesized compounds treated rats and standard remogliflozin treated rats were compared by ANOVA followed by dunnett test. Probability level p<0.05 was considered to be statistically significant. The Anti diabetic data of synthesized compounds were shown in Table-3 and figure-2.

Figure No: 2. BAR Diagram of Urinary Glucose Excretion (mg/body weight):

The result obtained in the preset investigation indicates that the anti hyperglycemic activity against the hyperglycemia with some derivatives was significant. From the table 3.2.1 it can be observed that the standard drug remogliflozin has shows anti hyperglycemic activity at 30mg/kg. Compounds 12f, 12h, 12i exhibited significant anti hyperglycemic activity at the concentration of 100mg/kg, while the other compounds showed moderate activity.

CONCLUSION:

Nine new compounds were synthesized by reacting oxazole substituted ethylacetoacetates (9a-9c) with different alkyl hydrazines to give various substituted pyrazole alcohols (10 a-10i) which in turn were reacted with bromoglucose (3)to yield R1, R2 substituted 2-(4-((2-(4-alkoxyphenyl)-5-methyloxazol-4-yl)methyl)-1-alkyl-5-methyl-1H-pyrazol-3-yloxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (12a-12i). The chemical structures of the synthesized compounds were characterized by means of IR, Mass and NMRspectroscopy.The compounds were screened for anti-diabetic activity by urinary glucose excretion method (UGE). Among the compounds tested, 12f, 12h and 12i have exhibited moderate anti-diabetic activity as that of standard drug, remogliflozin.These compounds can be further exploited to get the potent lead compound.

ACKNOWLEDGMENT:

The authors are thankful to Department of Pharmacy, JNTU, Hyderabad for continuous support.

AUTHORS’ CONTRIBUTIONS:

All the authors contributed equally in design and frame of the work, acquisition and interpretation of data and manuscript preparation, all authors have read the prepared manuscript and approved for the publication.

CONFLICT OF INTEREST:

No conflict of interest from all the authors

LIST OF ABBREVIATIONS:

MBTE- Methyl Tertiary Butyl Ether

TLC- Thin Layer Chromatography

NMR- Nuclear Magnetic Resonance

ANOVA- Analysis of Variance

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Received on 08.09.2020 Modified on 10.03.2021

Research J. Pharm.and Tech 2022; 15(2):591-597.

DOI: 10.52711/0974-360X.2022.00097