1, 0.05, 0.025, 0.0125, and 0.00625 ED50. The compounds were injected 60 min before the tests. The controls received the equivalent volume of the solvent. All tests performed as suggested by Vogel and Vogel (Vogel and Vogel, 1997) are generally accepted as basic HDAC inhibitors cancer in investigation of the central activity by behavioral methods. The acute toxicity of the compound was assessed in mice acc. to Litchfield and HSP990 purchase Wilcoxon method (Litchfield and Wilcoxon, 1949) as the ED50 calculated on the loss of the righting reflex within 48 h. In addition, the activity of the compounds was assessed in the following tests: (1) locomotor activity measured in photoresistor actometers for a single mouse for 30 min as spontaneous activity and amphetamine-induced

hyperactivity (mice received subcutaneusly (s.c.) 5 mg/kg of amphetamine 30 min before the test); (2) nociceptive reactions studied in the acetic acid (0.6 %) induced writhing test (the number of writhing episodes was measured for 10 min starting 5 min after i.p. administration of acid solution); NU7026 cell line (3) motor coordination evaluated in the rota-rod test; (4) body temperature in normothermic mice measured in the rectum of animals with a thermistor

thermometer; (5) pentylenetetrazole (110 mg/kg, s.c.)-induced convulsions were evaluated as the number of mice with clonic seizures, tonic convulsions, and dead animals; (6) head-twitch responses (HTR) after 5-hydroxytryptophan (L-5-HTP) recorded according to Corne et al. (1963) (mice received 5-HTP (230 mg/kg, i.p.) and the number of head-twitches was recorded in 6 two-minutes intervals (4–6, 14–16, 24–26, 34–36, 44–46, 54–56 min) during 1 h); (7) influence of naloxone (5 mg/kg, s.c.) on the antinociceptive effect of the compounds assessed in the writhing test. Statystical analysis The obtained data were calculated by χ2 test with Yates correction (PTZ-induced seizures) and one-way analysis of variance (ANOVA) (other tests). Post-hoc comparisons were carried out by means of Dunnett test. All results are presented in the figures as mean ± SEM.

A probability (p) value of 0.05 or less was considered as statistically significant. Results and Discussion Chemistry The compounds 3a–3x were obtained in one-step cyclocondensation of 1-aryl-4,5-dihydro-1H-imidazol-2-amines (1a–1l) diethyl 2-benzylmalonate Tenoxicam (2a) or diethyl 2-(2-chlorobenzyl)malonate (2b) under basic conditions (sodium methoxide), Fig. 4 cyclocondensation reaction. The cyclocondensation reaction of this type was earlier reported as a method of preparation of imidazo[1,2-a]pyrimidines (Matosiuk et al., 1996) as well as other derivatives of 1-aryl-4,5-dihydro-1H-imidazol-2-amines (Matosiuk et al., 2002a, b; Sztanke et al., 2005) and 1-aryl-4,5-dihydro-1H-imidazol-2-hydrazines (Sztanke, 2002, 2004). Reaction of imidazole-2-amines with electrophilic compounds represents one of the synthetic methods to build this heterocyclic system.