Synthesis and biological evaluation of some new pyridazinone derivatives

Figures & data

Table 1.  Anti-inflammatory activity of the pyridazinone derivatives. 19–34.

Compound	R	R`	% Inhibition ± SEM^a
			After 2 h	After 3 h
Control	—	—	—	—
Ibuprofen	—	—	75.23 ± 1.08	85.77 ± 0.75
19	4-Cl	H	23.09 ± 2.32***	36.99 ± 2.03***
20	4-Cl	4-Cl	54.52 ± 2.16***	71.95 ± 1.69***
21	4-Cl	4-NO2	29.99 ± 2.95***	44.51 ± 1.80***
22	4-Cl	4-OH	27.62 ± 2.26***	41.05 ± 1.65***
23	4-Cl	4-CH3	22.14 ± 3.08***	35.56 ± 2.54***
24	4-Cl	4-OCH3	27.62 ± 2.35***	42.47 ± 1.73***
25	4-Cl	4-OH; 3-OCH3	30.24 ± 2.84***	44.51 ± 2.17***
26	4-Cl	4-F	58.57 ± 1.04***	77.23 ± 0.68***
27	4-CH3	H	20.71 ± 1.97***	36.58 ± 1.83***
28	4-CH3	4-Cl	48.81 ± 2.25***	67.48 ± 1.68***
29	4-CH3	4-NO2	22.85 ± 2.33***	40.85 ± 2.61***
30	4-CH3	4-OH	21.19 ± 1.93***	38.41 ± 2.63***
31	4-CH3	4-CH3	31.67 ± 1.70***	53.86 ± 1.73***
32	4-CH3	4-OCH3	38.09 ± 2.14***	60.57 ± 1.65***
33	4-CH3	4-OH; 3-OCH3	30 ± 2.50***	46.13 ± 1.76***
34	4-CH3	4-F	46.19 ± 1.50***	68.90 ± 1.12***

*p < 0.05; **p < 0.01; ***p < 0.001.

^aRelative to the standard (ibuprofen) and data were analyzed by one-way ANOVA followed by Turkey test for n = 6.

Table 2.  Analgesic activity along with ulcerogenic and lipid peroxidation effect of the pyridazinone derivatives (20, 26, 28 and 34).

Compound	R	R`	Analgesic activity		Lipid peroxidation^c	Severity index^b
			Number of writhings^b	Inhibitory ratio^a (%)
Control	—	—	42.34 ± 1.45	—	0.239 ± 0.007^a***	0.00 ± 0.00
Ibuprofen	—	—	16.34 ± 0.67***	61.03 ± 2.56	0.597 ± 0.007^ab***	0.833 ± 0.105*
20	4-Cl	4-Cl	22.34 ± 0.67***	46.83 ± 2.78***	0.362 ± 0.008^ab***	0.083 ± 0.083
26	4-Cl	4-F	21.5 ± 0.76***	48.97 ± 2.33***	0.342 ± 0.004^ab***	0.083 ± 0.083
28	4-CH3	4-Cl	24.34 ± 0.88***	42.12 ± 3.10***	0.318 ± 0.018^ab***	0.25 ± 0.118
34	4-CH3	4-F	23.5 ± 0.76***	44.22 ± 2.42***	0.418 ± 0.005^ab***	0.25 ± 0.118

*p < 0.05; **p < 0.01; ***p < 0.001.

^aRelative to the standard (ibuprofen) and data were analyzed by one-way ANOVA followed by Turkey test for n = 6.

^bRelative to their respective control and data were analyzed by one-way ANOVA followed by Turkey test for n = 6.

^cLipid peroxidation activity is expressed as nanomoles of MDA per milligram of protein.

Figure 1.  Calibration standard curve for TBARS concentration.

Scheme 1.  Protocol for synthesis of title compounds.