Synthetic Approaches to a Carboranyl Thiouracil

Jg, Wilson

doi:10.1111/j.1600-0749.1989.tb00208.x

Cited by 16 publications

(6 citation statements)

References 25 publications

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“…Spectral data of 1a, 3a agreed with the literature [51]. Pyrimidine derivatives 8d, 8e, 8g were synthesized according to the known protocols [37,38]. Spectral parameters of 8e and 8g agreed with those presented in Refs.…”

Section: Starting ω-Alkyne Substituted Pyrimidinessupporting

confidence: 80%

“…6-Methyluracil derivatives 8g,h,i with a ω-alkyne substituent at the C5 atom were prepared in three steps by analogy with procedures earlier described [ 37 , 38 ]. Initially, ethylacetoacetate was alkylated in a solution of sodium in ethanol by treatment with (a) propargyl bromide to prepare ethyl 2-acetyl-4-pentynoate 8a ; (b) 5-iodo-pent-1-yne to prepare ethyl 2-acetyl-6-heptynoate 8b ; (c) 6-iodo-hex-1-yne to prepare ethyl 2-acetyl-7-octynyloate 8c (Scheme 1 ).…”

Section: Resultsmentioning

confidence: 99%

“…Spectral parameters of 8e and 8g agreed with those presented in Refs. [37,38], respectively. -4′-yn-1′-yl)quinazoline-2,4-dione (4b Ethyl 2-acetyl-7-octynoate (8c) Acetoacetic ester (20 g, 153.8 mol) was added dropwise with stirring to a solution of sodium (3.54 g, 153.9 mol) in 200 ml of ethanol at 0-5 °C, the mixture then was treated with 6-iodo-hex-1-yne (13.12 g, 160.0 mol) at temperature not above than 10 °C.…”

Section: Starting ω-Alkyne Substituted Pyrimidinesmentioning

confidence: 99%

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Synthesis of 1,2,3-triazolyl nucleoside analogues and their antiviral activity

et al. 2020

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Based on the fact that a search for influenza antivirals among nucleoside analogues has drawn very little attention of chemists, the present study reports the synthesis of a series of 1,2,3-triazolyl nucleoside analogues in which a pyrimidine fragment is attached to the ribofuranosyl-1,2,3-triazol-4-yl moiety by a polymethylene linker of variable length. Target compounds were prepared by the Cu alkyne-azide cycloaddition (CuAAC) reaction. Derivatives of uracil, 6-methyluracil, 3,6-dimethyluracil, thymine and quinazolin-2,4-dione with ω-alkyne substituent at the N1 (or N5) atom and azido 2,3,5-triO -acetyl-D-β-ribofuranoside were used as components of the CuAAC reaction. All compounds synthesized were evaluated for antiviral activity against influenza virus A/PR/8/34/(H1N1) and coxsackievirus B3. The best values of IC 50 (inhibiting concentration) and SI (selectivity index) were demonstrated by the lead compound 4i in which the 1,2,3-triazolylribofuranosyl fragment is attached to the N1 atom of the quinazoline-2,4-dione moiety via a butylene linker (IC 50 = 30 μM, SI = 24) and compound 8n in which the 1,2,3-triazolylribofuranosyl fragment is attached directly to the N5 atom of the 6-methyluracil moiety (IC 50 = 15 μM, SI = 5). According to theoretical calculations, the antiviral activity of the 1,2,3-triazolyl nucleoside analogues 4i and 8n against H1N1 (A/PR/8/34) influenza virus can be explained by their influence on the functioning of the polymerase acidic protein (PA) of RNA-dependent RNA polymerase (RdRP).

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Section: Starting ω-Alkyne Substituted Pyrimidinessupporting

confidence: 80%

Section: Resultsmentioning

confidence: 99%

Section: Starting ω-Alkyne Substituted Pyrimidinesmentioning

confidence: 99%

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Synthesis of 1,2,3-triazolyl nucleoside analogues and their antiviral activity

et al. 2020

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“…Several authors have shown that thiouracil is strongly taken up by melanotic melanoma in murine models (32,33), and in vitro experiments indicate that both high tyrosinase and melanin levels are required for enhanced incorporation (34). Boron containing thiouracils have been synthesised in Altstralia (Wilson 1989) and Germany (Gabel et a1 1990), and tested in syngeneic and nude mice models with murine and human melanomas . Therapeutic boron concentrations in the tumour and tumour to liver boron ratios of 10 have been achieved.…”

Section: E) Boron Containing Thiouracilmentioning

confidence: 99%

The Potential of Neutron Capture Therapy in the Management of Uncontrollable Localised Tumours

BSc.

1990

Australasian Radiology

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The role of Neutron Capture Therapy for the treatment of uncontrollable, localised tumours is examined. Several boron carrier biochemicals are already in use for the selective accumulation of boron in cancer cells, and therapeutic boron concentrations have been achieved in glioblastoma and melanoma in animal models and in patients. Local control of glioblastoma and subcutaneous melanoma has been reported after thermal neutron irradiation. Different neutron beam requirements apply for the treatment of these cancers, in the former case a thermal beam is adequate but a more penetrating epithermal beam is needed for the treatment of deep-seated tumours. A thermal facility for small animal irradiations is available in Australia, and the development of a patient thermal/epithermal facility is under active consideration.

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“…Several synthetic routes and false trails have been previously reported (Allen et al, 19861, and current efforts are directed to the conjugation of an alkyl decacarbor-any1 group attached to various positions on the ring (Wilson, 1989). While the synthesis of a carboranyl thiouracil is the primary objective, a thiouracil containing an alkynyl (i.e., a triple bond alkyl group) has been achieved.…”

Section: Boron Chemistrymentioning

confidence: 99%

Neutron Capture Therapy Research in Australia

Allen

1989

Pigment Cell Research

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Neutron capture therapy research in Australia has continued to grow since the first Australia-Japan workshop in April, 1986. The support base has broadened and the wide range of contributing laboratories includes universities, research institutes, and hospitals. Considerable progress has been made in boron chemistry--an accurate boron assay technique has been developed, boron analogues of chlorpromazine and thiouracil have been synthesised or nearly so, and decaborane conjugation with monoclonal antibodies has been achieved to the required loadings. In vitro cell survival experiments are proceeding in the Moata reactor using human melanoma and mouse cell lines incubated with enriched boronophenylalanine and boron tetraphenyl porphyrins. Electron microscopy examination of radiation damaged morphology shows considerable differences between cell lines. Progress with the nude mouse human melanoma model has been slow because of the lack of a reliable in vivo melanotic melanoma line, and the B16 mouse line is found to be more efficacious. Tailored beam calculations for the 10 MW HIFAR reactor indicate the difficulty of obtaining a suitable therapeutic beam because of the generated gamma dose in the beam filters. A new approach to NCT utilises the enormous cross section of 157Gd and the induced-Auger effect which has been shown to cause double strand breaks in circular DNA.

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Synthetic Approaches to a Carboranyl Thiouracil

Cited by 16 publications

References 25 publications

Synthesis of 1,2,3-triazolyl nucleoside analogues and their antiviral activity

Synthesis of 1,2,3-triazolyl nucleoside analogues and their antiviral activity

The Potential of Neutron Capture Therapy in the Management of Uncontrollable Localised Tumours

Neutron Capture Therapy Research in Australia

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