A series of pyrimido[1,2-a]benzimidazole and α-cyanocinnamic acid derivatives have been synthesized in the reactions of Schiff bases 2–7 with selected nitriles containing an active methylene group: malononitrile 8–12, cyanoacetamide 13–16, benzyl cyanide 17–21, benzoylacetonitrile 22–24, cyanoacetate methyl ester 25–28 and benzylacetamide 29. The structures 8–29 were confirmed by the results of elementary analysis and their IR, 1H-, 13C-NMR and MS spectra. The products 8–29 of various chemical structure pyrimido[1,2-a] benzimidazole 8–12, 14–16, 17–21, 23–24, 26 and α-cyanocinnamic acid derivatives 13, 22, 25, 27, 28 were obtained, which are of interest for biological studies or which can be substrates for further synthesis. The selected compounds 10, 13, 14, 17, 19, 21, 23–25 and 28 were screened for their antiproliferative activity in vitro against neoplastic and normal cell lines. The most active two compounds were: 2-(o-bromophenylene)-3-cyano-4-phenyl-1,2-dihydropyrimido[1,2-a]benzimidazole (24) and 3-cyano-4-phenyl-2-(2,4-dimethoxyphenyl)-1,2-dihydropyrimido[1,2-a]benzimidazole (23). However, similarly like cisplatin used as the control, they showed no selectivity towards cancer cells, by inhibiting proliferation of normal mouse fibroblasts in similar manner.

No abstract

The reaction of 2,2,4‐trimethyl‐1H‐2,3‐dihydro‐1,5‐benzodiazepine (1) with cinnamoyl chloride leading to the formation of 1‐cinnamoyl derivative 2 is described. Two novel benzodiazepines, 2,2,4‐trimethyl‐1H‐2,3,4,5‐tetrahydro‐1,5‐benzodiazepine (3) and 1‐cinnamoyl‐2,2,4‐trimethyl‐1H‐2,3,4,5‐tetrahydro‐1,5‐benzodiazepine (4), were synthesized by the reduction of 1 and 2 using NaBH4 in i‐PrOH and two other derivatives 5 and 6 were obtained by reaction of 4 with equimolar and dimolar quantity of cinnamoyl chloride, respectively. The structures of 1—6 were confirmed by analytical and spectral data (IR, 1H NMR, and MS). 7‐Carboxy‐2,2,4‐trimethyl‐1H‐2,3‐dihydro‐1,5‐benzodiazepine (7) was synthesized and its crystals were subjected to X‐ray analysis. Benzodiazepines 1—6 were evaluated for antiproliferative activity in vitro. Among the compounds tested, 4—6 exhibited cytotoxic activity against human cancer cell lines, namely SW707 (colon cancer), MCF‐7 (breast cancer), A549 (lung cancer), and HCV29T (bladder cancer).

The synthesis of two series of derivatives containing the quinazolinone-4 moiety is described. 3-Amino-2(1H)-thioxo-4(3H)-quinazolinone (1) was subjected to reactions with halogenoketones and halogenoaldehydes, leading to the production of the corresponding ketones, aldehydes, Schiff bases, and 6-oxo-1,4,5-thiadiazin[2,3-b]quinazoline derivatives. Subsequently, 1 was condensed with selected alpha, beta-unsaturated carbonyl compounds, aldehydes, ketones, acid chlorides, and esters. The compounds were tested for their potential activity in a model of humoral and cellular immune response. The tests showed that the compounds exhibited differential immunotropic activities. Of particular interest is compound 19, exhibiting a strong stimulatory activity with regard to cellular immune response and compound 16 exerting a strong inhibitory action in both types of the immune response.