- Antitumour imidazotetrazines. Part 36. Conversion of 5-aminoimidazole-4-carboxamide to imidazo[5,1-d][1,2,3,5]tetrazin-4(3H)-ones and imidazo[1,5-a][1,3,5]triazin-4(3H)-ones related in structure to the antitumour agents temozolomide and mitozolomide
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Novel 3-substituted imidazo[5,1-d][1,2,3,5]tetrazinones 3 have been prepared by two routes: reaction of 5-diazoimidazole-4-carboxamide 2 and isocyanates, and nitrosative cyclisation of 5-amino-1-carbamoylimidazole-4-carboxamides 7. The latter cyclisations do not proceed efficiently when the 1-carbamoyl group bears an electron-donating alkyl group. 5-Amino-1-carbamoylimidazole-4-carboxamides 7 cyclise with triethyl orthoformate or triethyl orthobenzoate to yield imidazo[1,5-a][1,3,5]triazinones 15. A 1H NMR study of the decomposition of 8-carbamoyl-3-ethylimidazo[5,1-d][1,2,3,5]tetrazin-4(3H)-one 3c in deuteriated phosphate buffer has shown that its ethylating capacity is attenuated by the unproductive generation of ethene. This observation explains why the ethylimidazotetrazine possesses weaker antitumour properties than the clinically-used congener temozolomide 3a.
- Wang, Yongfeng,Wheelhouse, Richard T.,Zhao, Linxiang,Langnel, David A. F.,Stevens, Malcolm F. G.
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p. 1669 - 1675
(2007/10/03)
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- Matrix Reactions of Oxygen Atoms with CH3CN. Infrared Spectra of HOCH2CN and CH3CNO
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Reactions of oxygen atoms and acetonitrile have been investigated in solid argon at 14-17 K.Primary photoproducts include hydroxyacetonitrile (HOCH2CN) and acetonitrile N-oxide (CH3CNO).Hydroxyacetonitrile forms hydrogen-bonded complexes with acetonitrile and acetonitrile N-oxide as the secondary products.Acetonitrile N-oxide is suggested to be formed by a simple bimolecular addition reaction of atomic oxygen with the nitrile nitrogen.The participation of O(1D) atoms is considered to increase the yield of hydroxyacetonitrile as compared to acetonitrile N-oxide via H-atom abstraction or insertion reactions.The spectral characteristics of hydroxyacetonitrile, acetonitrile N-oxide, and hydrogen-bonded hydroxyacetonitrile-acetonitrile complex isolated in argon matrices are given.
- Mielke, Zofia,Hawkins, Michael,Andrews, Lester
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p. 558 - 564
(2007/10/02)
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- Mass Spectral Characteristics of the Sulfur-containing Ketoxime Carbamates Thiofanox and Metabolites
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Deuterium labeling and high resolution mass spectroscopy have been used to determine the modes of electron impact fragmentation of 3,3-dimethyl-1-methylthio-2-butanone O-oxime, thiofanox and its metabolites, the sulfoxide and sulfone.The mass spectra of the corresponding oximes were also examined.The carbamates fragmented chiefly by two competing pathways-the loss of CH3N=C-O or the sulfur-containing moiety.The favored process was dependent on the oxidation state at sulfur.Several unusual rearrangements were noted.
- Corkins, H. G.,Mannion, J. J.,Storace, L.
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p. 185 - 191
(2007/10/02)
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