Synthesis and Analgesic Studies of Some New 2-pyrazolines

A new series of 2-pyrazolines (4a-j) were synthesized by reacting chalcones (3a-j) with phenyl hydrazine in the presence of pyridine and ethanol. All these compounds were characterized by means of their IR, HNMR spectral data and microanalyses. When these compounds were evaluated for analgesic activity, some of them were found to possess significant activity, when compared to standard drugs.

In view of these observations and in continuation of our research programme on the synthesis of chalcones and their derivatives 11 , we report herein the synthesis of some new pyrazoline derivatives which have been found to possess an interesting profile of analgesic activity.Synthetic methods for the preparation of pyrazoline derivatives (4a-j) are summarized in scheme-1.Chalcones were synthesized by the reaction of 3-acetyl-2,5dimethylfuran and various substitud aromatic and hetero cyclic aldehydes in presence of aq.KOH and ethanol.Pyrazolines were obtained in good yields by reacting chalcones (3a-j) with phenylhydrazine in hot pyridine.The structures of the various synthesized compounds were assigned on the basis of elemental analyses, IR and 1 H NMR spectral data.These compounds were also screened for their analgesic activity.

Material and Methods
All the chemicals used in the synthesis were obtained from standard commercial sources.Melting points were determined on an open capillary melting point apparatus and are uncorrected. 1H NMR spectra were recorded in CDCl 3 on Bruker WM 400 MHz spectrometer with TMS as internal standard.Infrared spectra were recorded (KBr) on a Perkin-Elmer AC-1 spectrophotometer.Micro analyses were performed on Carlo Erba E-1108 element analyzer and were within the ± 0.4% of the theoretical values.Reaction completion was identified by TLC using silica gel for TLC (Merck).All the chalcones have been purified by column chromatography performed on silica gel columns (100-200 mesh, Merck).

Analgesic Activity
Tail immersion test method 12,13 was adopted for the evaluation of analgesic activity of the test compounds.60 spraygue-dawley rats (M/S Gosh Enterprises, Calcutta, West Bengal, India) of either sex weighing between 180-200 g were used in the experiment and these were divided into 12 groups of 5 animals each and they were numbered individually.The animals were fasted for 24 hrs before administering the drug with water ad libitum.The group I was administered with only 2% v/v tween 80 solution which served as control.Group II was administered with 100 mg/kg body weight of ibuprofen suspension orally which served as a standard.Group III to group XII were administered with test compounds respectively, the dose being 100 mg/kg body weight selected on the basis of the standard drug used.All the animal tails were dipped into a beaker containing water maintained at 55 1 o C and the time taken for the animals to flick the tail from the hot water completely is recorded at 15 minutes, 30 minutes, 1 hour, 2 hours and 3 hours respectively.The percentage of protection in the control, standard and drug treated animals were recorded and calculated by using the formula.

% Analgesic activity (PAA) = [ (Rt/Rc) -1] x 100
Where Rt and Rc are the reaction time in test and control respectively.The results and statistical analysis of the analgesic activity of ibuprofen and the compounds tested are shown in Table 3 and Fig1

Table 1 .
. Physical data of the prepared compounds 4 (a-j).

Table 2 .
Spectral data of the prepared compounds 4 (a-j).