- Synthesis and evaluation of 6-Aza-2′-deoxyuridine monophosphate analogs as inhibitors of thymidylate synthases, and as substrates or inhibitors of thymidine monophosphate kinase in mycobacterium tuberculosis
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A series of 5-substituted analogs of 6-aza-2′-deoxyuridine 5′-monophosphate, 6-aza-dUMP, has been synthesized and evaluated as potential inhibitors of the two mycobacterial thymidylate synthases (i.e., a flavin-dependent thymidylate synthase, ThyX, and a classical thymidylate synthase, ThyA). Replacement of C(6) of the natural substrate dUMP by a N-atom in 6-aza-dUMP 1a led to a derivative with weak ThyX inhibitory activity (33% inhibition at 50 μM). Introduction of alkyl and aryl groups at C(5) of 1a resulted in complete loss of inhibitory activity, whereas the attachment of a 3-(octanamido)prop-1-ynyl side chain in derivative 3 retained the weak level of mycobacterial ThyX inhibition (40% inhibition at 50 μM). None of the synthesized derivatives displayed any significant inhibitory activity against mycobacterial ThyA. The compounds have also been evaluated as potential inhibitors of mycobacterial thymidine monophosphate kinase (TMPKmt). None of the derivatives showed any significant TMPKmt inhibition. However, replacement of C(6) of the natural substrate (dTMP) by a N-atom furnished 6-aza-dTMP (1b), which still was recognized as a substrate by TMPKmt. Copyright
- Koegler, Martin,Busson, Roger,De Jonghe, Steven,Rozenski, Jef,Van Belle, Kristien,Louat, Thierry,Munier-Lehmann, Helne,Herdewijn, Piet
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experimental part
p. 536 - 556
(2012/05/20)
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- PROCESS FOR STRAIGHTENING KERATIN FIBRES WITH A HEATING MEANS AND DENATURING AGENTS
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The invention relates to a process for straightening keratin fibres, comprising: (i) a step in which a straightening composition containing at least two denaturing agents is applied to the keratin fibres, (ii) a step in which the temperature of the keratin fibres is raised, using a heating means, to a temperature of between 110 and 250° C.
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- Synthesis and antimicrobial evaluation of 6-azauracil non-nucleosides
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The present study describes synthesis and antimicrobial evaluation of a series of novel 6-azauracil non-nucleosides. Reaction of silylated 6-azauracils with the appropriate chloroethers gave the corresponding non-nucleosides. 1-(Allyloxymethy)-6-azauracils and non-nucleosides bearing indanyl, cyclohexenyl, and cyclohexyl moieties were obtained via silylation of 6-azauracils followed by treatment with the appropriate acetals. Selected compounds were tested for their in vitro antimicrobial activity against a panel of standard strains of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Four compounds showed marked inhibitory activity particularly against the tested Gram-positive bacteria.
- El-Brollosy, Nasser R.
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scheme or table
p. 1483 - 1490
(2009/12/26)
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- Kinetic parameters and recognition of thymidine analogues with varying functional groups by thymidine phosphorylase
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Thymidine phosphorylase (TP, EC 2.4.2.4) recognized the structure of the substrate with high specificity, via both the base and the ribosyl moieties. The replacement of 3′-OH of thymidine markedly influenced its catalytic activity with TP. The conversion
- Hatano, Akihiko,Harano, Aiko,Takigawa, Yoshikatsu,Naramoto, Yasuhiro,Toda, Keisuke,Nakagomi, Yuuichi,Yamada, Hideyuki
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p. 3866 - 3870
(2008/12/20)
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- Comparative studies for selective deprotection of the N-arylideneamino moiety from heterocyclic amides: kinetic and theoretical studies. Part 2
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4-Benzylideneamino-1,2,4-triazine-3,5(2H,4H)-diones (2-5), 6-styryl-1,2,4-triazine-3,5(2H,4H)-dione (6), and 6-styryl-2,3-dihydro-3-thioxo-1,2,4-triazin-5(4H)-one (7) were synthesized and pyrolyzed in the gas phase. The kinetic effect of changing the substituent on the triazine ring from hydrogen to methyl, phenyl, and styryl was measured. Analyses of the pyrolyzates of 2-5 showed the elimination products to be benzonitrile and the triazine fragment, while the pyrolyzates of 6 and 7 reveal the formation of cis- and trans-cinnamonitriles. Theoretical study of the pyrolysis reactions of 2-5 using an ab initio SCF method was investigated.
- Al-Awadi, Nouria A.,Ibrahim, Yehia A.,Dib, Hicham H.,Ibrahim, Maher R.,George, Boby J.,Abdallah, Mariam R.
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p. 6214 - 6221
(2007/10/03)
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- 1,2,4-TRIAZINES DERIVATIVES, PREPARATION THEREOF AND USE THEREOF IN HUMAN THERAPEUTICS
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The invention relates to 3,5-dioxo-(2H,4H)-1,2,4-triazine derivatives of general formulae (I or II), in which in particular: R1 represents hydrogen, a linear or branched C1-C6 alkyl or alkoxy radical, a C5-C6 cycloalkyl radical, a phenyl (C1-C2) alkyl radical or a phenyl radical;-R2 represents hydrogen, a linear or branched Cl-C7alkyl radical, or a C1-C6 alkyl radical substituted with groups such as trifluoromethyl or phenyl;- linker represents a C2-C6 alkyl chain or -(CH2)n-O- (n = 2 to 5), - R3 represents a group of general formula below for which X = O, linker can be connected to the ortho-, meta- or para-positions of the aromatic of the group R3, R4, R5, R6, R7 and R8 represent hydrogen or fluorine, R9, Rio and R11 represent hydrogen or a linear or branched Cl-C5 alkyl group, in particular R9 and Rio represent the methyl group and R11 represents hydrogen or the ethyl group.
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Page/Page column 18
(2010/02/13)
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- Nucleoside process
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Process for producing 1-halo-2-deoxy-2-fluoroarabinofuranoside derivatives bearing protective ester groups from 1,3,5-tri-O-acylribofuranose; the 1-halo compounds are intermediates in the synthesis of therapeutically active nucleosidic compounds.
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