Synthesis and biological activity of 6-azacadeguomycin and certain 3,4,6-trisubstituted pyrazolo[3,4-d]pyrimidine ribonucleosides

Abstract

Several 3,4,6-trisubstituted pyrazolo[3,4-d]pyrimidine ribonucleosides were prepared and tested for their biological activity. High-temperature glycosylation of 3,6-dibromoallopurinol with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose in the presence of BF3 X OEt2, followed by ammonolysis, provided 6-amino-3-bromo-1-beta-D-ribofuranosylpyrazolo-[3,4-d]pyrimidin-4(5H)-on e. Similar glycosylation of either 3-bromo-4(5H)-oxopyrazolo [3,4-d]pyrimidin-6-yl methyl sulfoxide or 6-amino-3-bromopyrazolo [3,4-d]pyrimidin-4(5H)-one, and subsequent ammonolysis, also gave 7a. The structural assignment of 7a was on the basis of spectral studies, as well as its conversion to the reported guanosine analogue 1d. Application of this glycosylation procedure to 6-(methylthio)-4(5H)-oxopyrazolo[3,4-d]pyrimidine-3-carboxamide gave the corresponding N-1 glycosyl derivative. Dethiation and debenzoylation of 16a provided an alternate route to the recently reported 3-carbamoylallopurinol ribonucleoside thus confirming the structural assignment of 16a and the nucleosides derived therefrom. Oxidation of 16a and subsequent ammonolysis afforded 6-amino-1-beta-D-ribofuranosyl-4(5H)-oxopyrazolo[3, 4-d]pyrimidine-3-carboxamide. Alkaline treatment of 15a gave 6-azacadeguomycin. Acetylation of 15a, followed by dehydration with phosgene, provided the versatile intermediate 6-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-4(5H)-oxopyrazolo [3, 4-d]pyrimidine-3-carbonitrile. Deacetylation of 19 gave 6-amino-1-beta-D-ribofuranosyl-4(5H)-oxopyrazolo[3, 4-d]pyrimidine-3-carbonitrile. Reaction of 19 with H2S gave 6-amino-1-beta-D-ribofuranosyl-4(5H)-oxopyrazolo[3, 4-d]pyrimidine-3-thiocarboxamide. All of these compounds were tested in vitro against certain viruses and tumor cells. Among these compounds, the guanosine analogues 7a and 20a showed significant activity against measles in vitro and were found to exhibit moderate antitumor activity in vitro against L1210 and P388 leukemia. 6-Azacadeguomycin and all other compounds were inactive against the viruses and tumor cells tested in vitro.

Synthesis, Biological Activity and Cytotoxicity of New Fused Pyrazolo[1,5-<i>a</i>]pyrimidine from 5-Aminopyrazole Incorporated with <i>p</i>-Chloroaniline

“…Infrared spectra were recorded from KBr discs on FT-IR 8300 Shimadzu spectrometer. 1 H NMR and 13 C NMR spectra were recorded on FT-NMR 400 MHz Joel, ECP and FT-NMR 600 MHz Bruker, AVANCE III spectrometer operating at 400 MHz, and 600 MHz for 1 H NMR and at 100 MHz, 150 MHz for 13 C NMR in DMSO-d 6 as solvent and using TMS as internal standard. DIMS spectra were recorded on QP5050A Shimadzu apparatus.…”

“…Pyrazolopyrimidine derivatives constitute an interesting class of heterocycles because of their synthetic versatility, effective biological activities, and pharmacological importance as purine analogs [1][2][3][4][5]. Various related compounds of pyrazolopyrimidines have antitumor and antileukemic activities [6,7].…”

Synthesis and Antimicrobial Evaluation of Some Thiazole Derivatives

“…Heterocyclic compounds are widely distributed in nature and occupy a prominent place in medicinal chemistry as pharmaceuticals and drug intermediates [1][2][3]. They play a significant role in the metabolism of all living cells and many are clinically used for the treatment of various diseases.…”

Synthesis and biological evaluation of thieno[2,3-d]pyrimidine derivatives for anti-inflammatory, analgesic and ulcerogenic activity

“…[2,3-d] [1,2,4]triazolo [4,3-a]pyrimidin-5-one (4a). -Compound 4a was obtained from 2 (2.74 g, 0.01 mol) and N-phenylbenzene-carbohydrazonoyl chloride (2.31 g, 0.01 mol) as white needles, and crystallized from dimethylformamide.…”

“…-Product 4d was obtained from 2 (2.74 g, 0.01 mol) and 2-oxo-N-(4-nitrophenyl)-propane hydrazonoyl chloride (2.06 g, 0.01 mol) as pale red crystals, and crystallized from absolute ethanol. [2,3-d] [1,2,4]triazolo [4,3-a]pyrimidin-5-one-3-ethylcarboxylate (4e). -Compound 4e was obtained from 2 (2.74 g, 0.01 mol) and chloro-(phenylhydrazono)-ethyl acetate (2.27 g, 0.01 mol) as white powder, and crystallized from dimethylformamide.…”