Synthesis of 5-substituted uracils and 2,4-dimethoxypyrimidines by wittig olefination

Coutouli‐Argyropoulou, Evdoxia; Zachariadou, Christina

doi:10.1002/jhet.5570420615

Cited by 10 publications

(8 citation statements)

References 41 publications

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“…Regioselective alkylation at N1 was obtained also by exploiting the higher reactivity of the N1 position in thymine and iodouracil toward sterically hindered electrophiles (Fig. 2), which allowed direct synthesis of compounds 9 (according to Coutouli-Argyropoulou and Zachariadou, 2005) and 13 . The N1, N3-doubly alkylated compound 12 was obtained as a side product of thymine alkylation.…”

Section: Resultsmentioning

confidence: 99%

C(5) modified uracil derivatives showing antiproliferative and erythroid differentiation inducing activities on human chronic myelogenous leukemia K562 cells

Brognara

Lampronti

Breveglieri

et al. 2011

European Journal of Pharmacology

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The K562 cell line has been proposed as a useful experimental system to identify anti-tumor compounds acting by inducing terminal erythroid differentiation. K562 cells exhibit a low proportion of hemoglobin-synthesizing cells under standard cell growth conditions, but are able to undergo terminal erythroid differentiation when treated with a variety of anti-tumor compounds. In this paper we report a screening study on a set of different modified C(5) uracil derivatives for the evaluation of their antiproliferative effect in connection with erythroid differentiation pathways, and for defining a new class of drug candidates for the treatment of chronic myelogenous leukemia. Activity of the derivatives tested can be classified in two effect: an antiproliferative effect linked to a high level of erythroid differentiation activity and an antiproliferative effect without activation of gamma globin genes The highest antiproliferative effect and erythroid induction was shown by compound 9, a thymine derivative bearing a n-octyl chain on nitrogen N(1), whereas thymine did not show any effect, suggesting the importance of the linear alkyl chain in position N(1). To our knowledge this compound should be considered among the most efficient inducers of erythroid differentiation of K562 cells. This work is the starting point for the quest of more effective and specific drugs for the induction of terminal erythroid differentiation, for leading new insights in the treatment of neoplastic diseases with molecules acting by inducing differentiation rather than by simply exerting cytotoxic effects.

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Section: Resultsmentioning

confidence: 99%

C(5) modified uracil derivatives showing antiproliferative and erythroid differentiation inducing activities on human chronic myelogenous leukemia K562 cells

Brognara

Lampronti

Breveglieri

et al. 2011

European Journal of Pharmacology

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“…The IR spectra were measured with a Shimadzu FTIR 8300 instrument. NMR spectra were recorded with a Bruker DPX 300 and Bruker Avance AV 500 at 300 MHz for 1 H and 75.47 MHz for 13 C and 500 MHz for 1 H and 125.72 MHz for 13 C, respectively. Chemical shifts are given in δ units (ppm) to residual CHCl 3 (7.26 and 77.0 ppm, respectively) and DMSO (2.50 and 39.5 ppm, respectively).…”

Section: Methodsmentioning

confidence: 99%

“…Following the general procedure, the reaction with the ethyl propanoate 1b gave 1.80 g of a white solid, 78 % yield; m.p. 51-52°C (MeOH 13…”

Section: -Ethoxy-5-methyl-26-bis(methylthio)pyrimidine (4b)mentioning

confidence: 99%

“…137-138°C (MeOH). C 14 Supporting Information (see also the footnote on the first page of this article): 1 H NMR, 13 C NMR and DEPT spectra of compounds 4b-f, 5a, 5c, 5d, 6, 11b-f, 12b, 12e, 13e, 14b, 15b and 15d.…”

Section: -Ethoxy-26-bis(methylsulfonyl)-5-phenylpyrimidine (12e)mentioning

confidence: 99%

“…[1,[10][11][12] Recently, 2,4-dimethoxypyrimidine derivatives have been prepared from uracils by Wittig olefination. [13] In spite of their importance, there is no synthetic method to prepare polyalkoxypyrimidines from readily available starting materials with high yields in a few reaction steps.…”

Section: Introductionmentioning

confidence: 99%

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A New Synthetic Route to Polyalkoxypyrimidines Based on the Reaction of Esters and Methyl Thiocyanate

et al. 2006

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The reaction of aliphatic esters with methyl thiocyanate and triflic anhydride affords substituted 4‐alkoxy‐2,6‐bis(methylthio)pyrimidines with minor amounts of substituted S‐methyl N‐alkanoylthiocarbamates. The structure of the starting ester appears to determine the ratio of final products. Methylthio groups on the pyrimidine ring can be easily converted into methylsulfonyl groups by oxidation. Controlled substitution of one or both methylsulfonyl groups leads to the formation of aminodialkoxy‐ and trialkoxypyrimidines. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

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