18493-83-9Relevant articles and documents
Synthesis of acyclic nucleoside phosphonates targeting flavin-dependent thymidylate synthase in Mycobacterium tuberculosis
Agrofoglio, Luigi A.,Becker, Hubert F.,Biteau, Nicolas G.,Lambry, Jean-Christophe,Myllykallio, Hannu,Roy, Vincent
, (2021/08/16)
Flavin-Dependent Thymidylate Synthase (FDTS) encoded by ThyX gene was discovered as a new class of thymidylate synthase involved in the de novo synthesis of dTMP named only in 30 % of human pathogenic bacteria. This target was pursed for the development of new antibacterial agents against multiresistant pathogens. We have developed a new class of ANPs based on the mimic of two natural's cofactors (dUMP and FAD) as inhibitors against Mycobacterium tuberculosis ThyX. Several synthetic efforts were performed to optimize regioselective N1-alkylation, cross-coupling metathesis and Sonogashira cross-coupling. Compound 19c showed a poor 31.8% inhibitory effect on ThyX at 200 μM.
NOVEL HETEROCYCLIC COMPOUNDS AND USE THEREOF IN MEDICINE AND IN COSMETICS
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Paragraph 0583, (2018/03/25)
The invention relates to novel heterocyclic compounds of general formula (I), as well as their pharmaceutically acceptable salts, and their enantiomers. The invention also relates to the use thereof as a medicinal product, preferably in the prevention and/or treatment of inflammatory diseases with a neurogenic component or use thereof as a cosmetic. The compounds of the present invention act as antagonists of the CGRP-R receptor.
Synthesis of modified uracil and cytosine nucleobases using a microwave-assisted method
Burgula, Laxmi Narayana,Radhakrishnan,Kundu, Lal Mohan
supporting information; experimental part, p. 2639 - 2642 (2012/06/30)
Modified nucleobases and nucleic acids have found many biological and pharmaceutical applications. Here we report a microwave-directed synthesis of a variety of modified uracil and cytosine nucleobases with high yields under solvent-free conditions. The reaction yields were further improved by addition of Lewis acid. The crystal structures of 5-isopropyl-6-methyluracil and 6-phenyluracil were also determined.
DNA-protein cross-linking: Model systems for pyrimidine-aromatic amino acid cross-linking
Sun, Guangxing,Fecko, Christopher J.,Nicewonger, Robert B.,Webb, Watt W.,Begley, Tadhg P.
, p. 681 - 683 (2007/10/03)
We have synthesized simple model systems to explore the possibility of photo-cross-linking between the pyrimidine bases and the side chains of the aromatic amino acids. Thymine/phenylalanine and thymine/tyrosine models gave cross-links, and thymine/tryptophan models gave complex mixtures; the cytosine/phenylalanine model was unreactive. The quantum yields for the model cross-linking reactions were 18-46 times smaller than those for thymine dimer formation. Biphotonic excitation contributes little to the yield of these reactions.
Inhibition of uridine phosphorylase: Synthesis and structure-activity relationships of aryl-substituted 5-benzyluracils and 1-[(2- hydroxyethoxy)methyl]-5-benzyluracils
Orr,Musso,Boswell,Kelley,Joyner,Davis,Baccanari
, p. 3850 - 3856 (2007/10/02)
A series of 1-[(2-hydroxyethoxy)methyl]-5-benzyluracils were synthesized and tested for inhibition of murine liver uridine phosphorylase (UrdPase). Inhibitors of UrdPase are reported to enhance the chemotherapeutic utility of 5-fluoro-2'-deoxyuridine and 5-fluorouracil and to ameliorate zidovudine- induced anemia in animal models. We prepared a series of 5-aryl-substituted analogues of 5-benzylacyclouridine (BAU), a good inhibitor of UrdPase (IC50 of 0.46 μM), to develop a compound with enhanced potency and improved pharmacokinetics. The first phase of structure-activity relationship studies on a series of 32 aryl-substituted 5-benzyluracils found several 5-(3- alkoxybenzyl) analogues of 5-benzyluracil with enhanced potency. The acyclovir side chain, the (2-hydroxyethoxy)methyl group, was substituted on the more potent aryl-substituted 5-benzyluracils. The two most potent compounds, 10y (3-propoxy) and 10dd (3-sec-butoxy), were inhibitors of UrdPase with IC50s of 0.047 and 0.027 μM, respectively. Six compounds were tested in vivo for effects on steady-state concentrations of circulating uridine in rats. Plasma uridine levels were elevated 3-9-fold by compound levels that ranged from 8 to 50 μM.
Derivatives of 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-5-phenyluracil and 5-benzyluracil synthesis and biological properties
Dziewiszek,Schinazi,Chou,Su,Dzik,Rode,Watanabe
, p. 77 - 94 (2007/10/02)
A number of 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil and -cytosine nucleosides substituted at the 5 position with a nitrophenyl or nitrobenzyl group were synthesized from 5-phenyl- and 5-benzyluracil via condensation of the fluorinated sugar, followed by nitration. The corresponding amino analogues were also prepared by reduction of the nitro nucleosides. The uracil nucleosides were converted into the corresponding cytosine nucleosides by way of the triazole intermediates. None of these nucleosides exhibited significant activity against herpes simplex virus type 1 in Vero cells. However, cytosine nucleosides containing the o-nitrophenyl, p-nitrophenyl, p- nitrobenzyl or p-aminobenzyl substituent were found to be toxic (even at 1 μM) to uninfected Vero cells, although they were essentially nontoxic in HL- 60 cells. The 5'-monophosphates of the uracil nucleosides were inhibitors of the reaction catalyzed by purified Ehrlich ascites carcinoma thymidylate synthase, the 5-phenyluracil nucleotides causing a strong inhibition, competitive vs dUMP, described by the K(i) value of 0.01 μM.
Process for preparing uracil derivatives
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, (2008/06/13)
The present invention relates to a novel process for preparing uracil derivatives useful as intermediates in the synthesis of uridines having antiviral or antitumor activity or useful as coadjuvants in antiviral therapy, characterized by converting a compound of the formula II into its mesylate derivative of the formula III which is the reduced to give the desired compound of the formula I: STR1 in which R1 is H, halogen, alkyl, aryl or aralkyl.
SYNTHESIS OF 5-ALKYL SUBSTITUTED URACIL DERIVATIVES FROM BARBITURIC ACID
Candiani, Ilaria,Cabri, Walter,Bedeschi, Angelo,Martinengo, Tiziano,Penco, Sergio
, p. 875 - 879 (2007/10/02)
A new two step synthesis of 5-alkyluracil derivatives from barbituric acids is described.Regioselective mono O-mesylation of barbituric acids, followed by desulfonylation under reductive conditions, afforded uracils in high overall yield.The reductive desulfonylation step is also discussed.
REDUCTIVE DEBROMINATION OF 5-BROMOURACILS BY 1-BENZYL-1,4-DIHYDRONICOTINAMIDE
Sako, Magoichi,Hirota, Kosaku,Maki, Yoshifumi
, p. 3919 - 3922 (2007/10/02)
N(1)-Unsubstituted 5-bromouracils with or without a substituent in position 6 undergo reductive debromination with ease most likely via a one-electron transfer process upon treatment with 1-benzyl-1,4-dihydronicotinamide under thermal conditions.
