A number of diversely functionalized derivatives of a novel [1,3]selenazolo[4,5‐d]pyrimidine have been synthesized through heterocyclization of some 2,4,5‐trisubstituted‐1,3‐selenazoles with orthoesters in refluxing acetic acid. The synthetic compounds were evaluated for their antimicrobial activity against a panel of microorganisms including Gram‐negative bacteria, Gram‐positive bacteria, and pathogenic fungi. The antifungal results revealed that the new selenium‐containing heterocycles were as good as or sometimes better than terbinafine and fluconazole. The in vitro anticancer activities of aforementioned heterocyclic compounds were screened against human breast carcinoma MCF‐7 and HeLa cervical cancer cells as well as HDF (human dermal fibroblast) normal cells. Antiproliferative results indicated that compounds with piperidine moiety on MCF‐7 cells and with morpholine moiety on HeLa cells exhibited well broad‐spectrum of anticancer activities with 397, 298 and 235 μM and 533, 390 and 204 μM of IC50 values after 24, 48 and 72 h of treatments, respectively, while they had no significant toxic effects on normal cells.

Pyrazolo [3,4-d]pyrimidines have considerable chemical and pharmacological importance because of their structural similarities to purine. They have been reported to act as cyclin dependent kinase, 1,2 tyrosine kinase 3 and potent xanthine oxidase inhibitors. 4 Other biological activities such as antibacterial, antifungal, 5-7 antiphlogistic, antitumor, 8, 9 herbicidal, 10 CNS (central nervous system) depressants 11 and neuroleptic agents 12 have been ascribed to pyrazolopyrimidines.Pyrazolotriazolopyrimidines are another class of fused heterocycles with interesting pharmacological activities. [13][14][15][16] There are several reports on the synthesis and chemistry of these compounds in the literature. [13][14][15][16][17][18][19][20][21][22][23][24] Among them the pyrazolo [4,3-e][1,2,4]triazolo[4,3-c]pyrimidine ring system has received less attention and very little is known about the synthesis and properties of these compounds. 13,[22][23][24] We now describe a protocol to synthesise various new derivatives of pyrazolo [4,3-e][1,2,4]triazolo[4,3-c]pyrimidine as well as the structural characterisations by spectral and microanalytical data. Results and discussionOur approach is based on using pyrazolo [3,4-d]pyrimidines 1a-c as starting materials. 25 Treatment of compounds 1a-c in boiling POCl 3 gave the corresponding 4-chlorinated pyrazolo [3,4-d]pyrimidines 2a-c. Compounds 2a-c were then reacted with hydrazine hydrate at room temperature to obtain the hydrazino derivatives 3a-c. The latter compounds subsequently underwent a cyclocondensation reaction with various triethyl orthoesters in acetic acid on heating under reflux to give the desired tricyclic pyrazolo [4,3-e][1,2,4] triazolo [4,3-c]pyrimidines 4a-i in good yields. (Scheme 1)The structural assignments of compounds 4a-i were confirmed by spectroscopic and microanalytical data. For example, the IR spectrum of compound 3a showed the stretching vibration bands at n max 3407, 3313 cm -1 (NH 2 ) and 3284 cm -1 (NH) whilst the IR spectrum of compound 4c revealed the absence of an NH moiety. The 1 H NMR spectrum of compound 4c also showed a multiplet signal in the range 1.45-1.52 ppm and two quartet signals at 3.04 and 3.41 ppm due to two ethyl groups, a multiplet signal around 7. 26-8.15 ppm

A straightforward approach for the regioselective synthesis of highly functionalized pyrazolo[5,1‐b]purine from the annulation of 6‐bromo‐3‐cyano‐2‐(ethylthio)‐5‐methyl‐7‐oxo‐6,7‐dihydropyrazolo[1,5‐a]pyrimidine with thiourea as a bisnucleophilic reagent under reflux condition in CH3CN in the presence of Et3N has been developed. The N‐alkylation of the synthesis compound was also accomplished. The true regioisomer was determined by 2D‐NOESY NMR spectroscopy, as well.

Several derivatives of the novel benzo [b]pyrazolo[5′,1′:2,3]pyrimido[4,5-e][1,4]thiazine ring system have been synthesized through the one-pot cyclocondensation of 6-bromo-7-chloro-2-(ethylthio)-5-methylpyrazolo[1,5-a] pyrimidine-3-carbonitrile (4) with o-aminothiophenol in the presence of Et 3 N in CH 3 CN. The true regio isomer (5) was also determined by X-ray crystallographic analysis. The N-alkylation of the synthesized compound (5) was also accomplished.

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