- Anti-HIV-Active Nucleoside Triphosphate Prodrugs
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We disclose a study on nucleoside triphosphate (NTP) analogues in which the γ-phosphate is covalently modified by two different biodegradable masking units and d4T as nucleoside analogue that enable the delivery of d4TTP with high selectivity in phosphate buffer (pH 7.3) and by enzyme-triggered reactions in human CD4+ T-lymphocyte CEM cell extracts. This allows the bypass of all steps normally needed in the intracellular phosphorylation. These TriPPPro-nucleotides comprising an acyloxybenzyl (AB; ester) or an alkoxycarbonyloxybenzyl (ACB; carbonate) in combination with an ACB moiety are described as NTP delivery systems. The introduction of these two different groups led to the selective formation of γ-(ACB)-d4TTPs by chemical hydrolysis and in particular by cell extract enzymes. γ-(AB)-d4TTPs are faster cleaved than γ-(ACB)-d4TTPs. In antiviral assays, the compounds are highly active against HIV-1 and HIV-2 in wild-type CEM/O cells and more importantly in thymidine kinase-deficient CD4+ T-cells (CEM/TK-).
- Jia, Xiao,Schols, Dominique,Meier, Chris
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p. 6003 - 6027
(2020/07/10)
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- Compounds having reversible inhibiting activity of carnitine palmitoyl-transferase
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Compounds of formula (I) wherein the groups are as defined in the description are disclosed. The compounds of formula (I) are endowed with reversible inhibiting activity of carnitine palmitoyl-transferase and are useful in the preparation of medicaments useful in the pathologies related to a hyperactivity of carnitine palmitoyl-transferase, such as hyperglycemia, diabetes and pathologies related thereto, heart failure, ischemia.
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- Method for stabilizing synthetic thermoplastic materials against thermal degradation
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The present invention relates to a novel method for stabilizing synthetic thermoplastic materials against thermal degradation, which comprises incorporating in said materials one or more compounds of the formula (I) STR1 in which R1 is unsubstituted or substituted phenyl, n is e.g. 1, 2 or 3, and, when n is 1, R2 is e.g. --COR3, --COOR4 or --CO-N(R5)R6 in which R3 is e.g. C4 -C17 alkyl, R4 is e.g. C4 -C18 alkyl, cyclohexyl or t-butylcyclohexyl, R5 and R6 which can be identical or different are e.g. C2 -C8 alkyl or cyclohexyl, and, when n is 2, R2 is e.g. --CO--R10 --OC, --COO-R11 --OOC-- or --CONH--R12 --NHCO- in which R10 is e.g. C2 -C8 alkylene, R11 is e.g. C4 -C6 alkylene and R12 is e.g. C4 -C6 alkylene, and, when n is 3, R2 is e.g. benzenetricarbonyl. Several compounds of the formula (I) are new.
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- Unsaturated cyclic ureas as new nontoxic biodegradable transdermal penetration enhancers I: Synthesis
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A new concept was implemented to reduce the toxicity of some new biodegradable transdermal penetration enhancers. These enhancers consist of 1-alkyl-4-imidazolin-2-one and a long-chain alkyl ester group at the N-3 position. The synthesis involves N-alkylation of the parent compound with soft alkylating agents which were prepared in high yields by an improved method. A phase transfer catalysis technique using KOH as the base, tetrabutylammonium bromide as the catalyst, and toluene as the solvent was found to be most effective in the N-alkylation step.
- Wong,Hungtington,Konishi,Rytting,Higuchi
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p. 967 - 971
(2007/10/02)
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