As a part of systematic investigation of synthesis and biologically active compounds of thiazolidine (TZD) derivatives containing pyrazole ring system, several new pyrazole-TZD derivatives 8aÀd and 9aÀd have been synthesized. Compounds 8aÀd were prepared from N-substituted TZDs 6aÀd and 1H-pyrazole-4carboxaldehyde 7 by Knoevenagel-type reaction. Treatment of 8aÀd with sodium hydride at room temperature caused dimerization reaction to afford the corresponding spirocompounds 9aÀd. All the synthesized compounds were characterized by spectroscopic analysis. In vitro, the synthesized compounds 8aÀd and 9aÀd were tested for their growth inhibitory activity in A549 lung cancer, B16F10 murine melanoma, and HeLa human uterine carcinoma cells and for their differentiation of 3T3-L1 preadipocytes to adipocytes. The results showed that compound 8c possessed growth inhibitory effect of B16F10 cells (IC 50 ¼ 27 lM) and compounds 9c,d had induction effect on the differentiation of 3T3-L1 preadipocytes.

An approach to pyrano [2,3-c]pyrazoles starting from spirocyclopropanepyrazoles via a ring-opening/ cyanomethylation and intramolecular cyclization is described. Reactions of spirocyclopropanepyrazoles 1a-d with chloroacetonitrile in the presence of sodium hydride gave the corresponding cyanomethoxypyrazoles 4a-d. Treatment of 4a-d with sodium hydride at room temperature caused intramolecular Michael addition reaction to afford the corresponding pyrano[2,3-c]pyrazoles 5a-d.

A novel synthetic route to 4‐pyridazineacetic acids 10–12 has been achieved by the ring‐expansion reaction of N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7–9. 1H‐Pyrazole‐4‐acetic acids 1–3 were reacted with iodoacetonitrile in the presence of triethylamine in refluxing acetonitrile to give the corresponding C‐cyanomethylated 1H‐pyrazole‐4‐acetic acids 4–6 as major products together with N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7 and 8 as minor products. On the other hand, reactions of 1 and 3 with chloroacetonitrile in the presence of triethylamine in refluxing chloroform afforded the corresponding N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7 and 9 as major products. Thermal treatment of 7–9 with sodium hydride in N,N‐dimethylformamide caused ring expansion to yield the corresponding 4‐pyridazineacetic acids 10–12.

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in Wiley Online Library (wileyonlinelibrary.com).Dihydropyridazinones 4a,b, N-substituted dihydropyrazoles 5b-d, and O-substituted pyrazoles 6a-d have been synthesized starting from spirocyclopropanepyrazole derivative 2. Treatment of 2 with achloro esters, e.g., methyl chloroacetate, ethyl chloroacetate, isopropyl chloroacetate, and tert-butyl chloroacetate, in potassium carbonate/sodium iodide system caused ring opening and subsequent C-or N-attack nucleophilic substitution to give the corresponding dihydropyridazinones 4a,b and N-substituted dihydropyrazoles 5b-d. On the other hand, in the absence of sodium iodide, O-substituted pyrazoles 6a-d were obtained from 2 via an O-attack nucleophilic substitution.