Synthesis and Anti-Inflammatory Activity of Some New Pyrimidine Derivatives

 

Ramesh  B.1* and Babitha S.2

1Dept. of Pharmaceutical Chemistry, Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur-572102. Karnataka

1Dept. of Pharmacology, Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur-572102. Karnataka

*Corresponding Author E-mail: babithamurthy@gmail.com

 

ABSTRACT

Some new pyrimidine derivatives were synthesized by reacting chalcones of 2-acetyl thiophene with guanidine hydrochloride in the presence of alcohol. The synthesized compounds were identified by spectral data and screened for anti-inflammatory activity. Some of these compounds showed moderate to considerable anti-inflammatory activity.

 

KEYWORDS: Synthesis, Pyrimidines, Anti-inflammatory activity.

 

 


INTRODUCTION:

Compounds with pyrimidine structures are known to possess antimicrobial1,2 anti-inflammatory3, cytotoxic,4,5 anti-cancer activities6,7. In the present study some new pyrimidine derivatives (1 to 5) have been synthesized by the reaction of chalcones of 2-acetyl thiophene and guanidine hydrochloride. The structures of the various synthesized compounds are assigned on the basis of elemental analysis, IR and 1H NMR spectral data. These compounds were also screened for their anti-inflammatory activity.

 

EXPERIMENTAL:

Melting points were determined on a capillary melting point apparatus and are uncorrected. 1H NMR spectra was recorded in the indicated solvent on Bruker WM 400 MHz spectrometer with TMS as internal standard. Infrared spectra were recorded in KBr on Perkin-Elmer AC-1 spectrophotometer. Microanalyses were performed on Carlo Erba EA-1108 element analyzer and were within the ± 0.5% of the theoretical values. Column chromatography was performed on silica gel (Merck, 60-120 mesh).

 

General procedure for the preparation of pyrimidine derivatives (1-5)

A mixture of  chalcones of 2-acetyl thiophene (0.001 mol) and guanidine hydrochloride (500 mg) in absolute ethanol (10 ml) were reflexed on a waterbath for 6 hours. The solvent was completely evaporated and the residue was poured into ice cold water. The precipitated solid was collected by filtration and crystallized from suitable solvent to give the pyrimidine derivative.

 

Anti-inflammatory activity:

Five compounds (1-5) were screened for anti-inflammatory activity. Male albino rats weighing between 200-250g were used for the experiment. Carrageenan induced paw oedema method described by Singh and Ghosh8 was followed for the acute anti-inflammatory model. (Table-3)

 

RESULTS AND DISCUSSION:

The screening results revealed that the compounds (1-5) exhibited moderate to considerable activity when compared with reference standard aceclofenac. It was found that compounds 1, 2, 3 and 4 showed maximum activity and this may be due to the presence of 3, 4, 5 – trimethoxy, 4-dimethyl amino, 3,4-dimethoxy and 4-nitro groups whereas other compound 5 showed moderate activity.

 

ACKNOWLEDGEMENTS:

We are thankful to the Head, Sophisticated Instrumentation Facility, Indian Institute of Sciences, Bangalore for 1H NMR spectra and to Sipra Laboratories, Hyderabad for IR spectra.

 

Scheme 1 : Synthesis of some new pyrimidine derivatives

 

Table 1. Physical data of compounds (1-5)

Compound

M.F.

M.P

(°C)

Yield

(%)

Elemental analyses (%)

C

H

N

Calcd

Found

Calcd

Found

Calcd

Found

(1)

(2)

(3)

(4)

(5)

C17H17O3SN3

C16H16SN4

C16H15N3SO2

C14H10O2N4S

C13H10N4S

150

120

143

232

198

72

76

82

76

64

41.46

42.10

61.39

57.93

61.47

41.45

42.16

61.34

56.37

61.41

41.46

42.10

4.83

3.44

3.96

41.39

42.08

4.79

3.35

3.93

9.72

14.10

13.42

16.55

22.05

9.81

14.14

13.41

16.23

22.04

 

Table 2. Spectral data of the compounds (1-5)

Compound

IR (KBr, cm-1)

1H NMR (CDCl3, ppm)

(1)

3361 (-NH2), 1601 (C=N),

1572 (C=C),

1119 (-OCH3),

704 (C-S).

5.22 (2H, brs, -NH2),

3.91-3.99 (9H, S, =3X-OCH3),

7.17 (1H, m, C-411-H),

7.80 (1H, d, C-511-H), 7.50 (1H, d, C-311-H),

7.29 (2H, S, C-21-H, C-61-H),

7.30 (1H, S, C-5-H).

 

(2)

3338 (-NH2), 1633 (C=N),

1588 (C=C),

1185 (-N(CH3)2),

660 (C-S).

3.10 (6H, S, -N(CH3)2),

5.40 (2H, brs, -NH2), 7.15 (1H, m, C-411, H),

8.01 (2H, d, C-31-H, C-51-H),

6.75 (2H, d, C-21-H, C-61-H),

7.79 (1H, d, C-511-H), 7.48 91H, d, C-311-H),

7.28 (1H, S, C-5-H).

 

(3)

3414 (-NH2), 1641 (C=N),

1519 (C=C),

1145 (-OCH3),

735 (C-S).

3.94 (3H, S,C-3-OCH3),

3.99 (3H, S, C-4-OCH3),

5.23 (2H, brs, NH2), 6.95 (1H, d, Ar-H),

7.13 (1H, t, Ar-H), 7.15 (1H, S, Ar-H),

7.31 (2H, S, C-5-H), 7.47 (1H, d, Ar-H),

7.60 (1H, d, Ar-H), 7.68 (1H, d, Ar-H).

 

(4)

3413 (-NH2), 1605 (C=N),

1344 (C=O), 688 (N=O).

5.26 (2H, brs, NH2), 7.17 (1H, m, Ar-H),

7.38 (1H, S, C-5-H), 7.52 (1H, d, Ar-H),

7.81 (1H, d, Ar-H), 8.20 (2H, d, Ar-H),

8.33 (2H, d, Ar-H).

 

(5)

3335 (-NH2), 1635 (C=N),

1570 (C=C), 680 (C-S).

5.22 (2H, brs, NH2), 7.16 (1H, m, Ar-H),

7.38 (1H, S, C-5-H), 7.51 (1H, d, Ar-H),

7.80 (1H, d, Ar-H), 7.90 (2H, d, Ar-H),

8.76 (2H, d, Ar-H).

 

Table 3. Anti-inflammatory activity of the compounds (1-5)

Compound

% increase in paw thickness of various time intervals

0.5 hr

01 hr

2 Hr

3 hr

4 hr

6 hr

Standard

Control

1

2

3

4

5

20.26 ± 0.64

-

19.25 ± 1.02

18.43 ± 1.86

18.43 ± 1.32

20.79 ± 1.86

20.43 ± 1.83

23.95 ± 0.66

-

26.71 ± 2.31

26.66 ± 3.27*

26.83 ± 1.86

32.61 ± 3.27*

28.33 ± 2.32*

58.08 ± 1.84

-

42.27 ± 1.08

56.99 ± 3.96**

57.87 ± 3.17*

61.34 ± 3.96**

53.41 ± 3.98**

67.93 ± 1.65

-

63.62 ± 1.86

78.21 ± 3.27

78.15 ± 3.89**

79.21 ± 3.27

78.42 ± 1.83

97.09 ± 1.95

-

81.24 ± 2.27*

88.99 ± 3.28**

89.26 ± 3.01

88.29 ± 3.28**

88.17 ± 2.37

98.98 ± 1.98

-

98.27 ± 2.18

93.14 ± 1.54

93.12 ± 1.96

95.53 ± 1.54

92.32 ± 1.35

Values are expressed as mean ± SEM (n=5), * P < 0.05, ** P < 0.01, *** P < 0.001 compared to controls. Student’s t-test.

 


 

 


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Received on 11.07.2009       Modified on 14.09.2009

Accepted on 10.10.2009      © RJPT All right reserved

Research J. Pharm. and Tech.2 (4): Oct.-Dec. 2009; Page 830-832