- Synthesis of acyclic nucleoside phosphonates targeting flavin-dependent thymidylate synthase in Mycobacterium tuberculosis
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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.
- Agrofoglio, Luigi A.,Becker, Hubert F.,Biteau, Nicolas G.,Lambry, Jean-Christophe,Myllykallio, Hannu,Roy, Vincent
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- 5-arylaminouracil derivatives: New inhibitors of Mycobacterium tuberculosis
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Three series of 5-arylaminouracil derivatives, including 5-(phenylamino)uracils, 1-(4′-hydroxy-2′-cyclopenten-1′-yl)-5-(phenylamino)uracils, and 1,3-di-(4′-hydroxy-2′-cyclopenten-1′-yl)-5-(phenylamino)uracils, were synthesized and screened for potential antimicrobial activity. Most of compounds had a negative effect on the growth of the Mycobacterium tuberculosis H37Rv strain, with 100% inhibition observed at concentrations between 5 and 40 μg/mL. Of those, 1-(4′-hydroxy-2′-cyclopenten-1′-yl)-3-(4?-hydroxy-2?-cyclopenten-1?-yl)-5-(4″-butyloxyphenylamino)uracil proved to be the most active among tested compounds against the M. tuberculosis multidrug-resistant strain MS-115 (MIC90 5 μg/mL). In addition, the thymidylate kinase of M. tuberculosis was evaluated as a possible enzymatic target. Three series of 5-arylaminouracil derivatives were synthesized and screened for potential antimicrobial activity. Most of compounds had a negative effect on the growth of the M. tuberculosis H37Rv strain, with 100% inhibition observed at concentrations between 5 and 40 μg/mL. Of those, 1-(4′-hydroxy-2′-cyclopenten-1′-yl)-3-(4?-hydroxy-2?-cyclopenten-1?-yl)-5-(4″-butyloxyphenylamino)uracil proved to be the most active among tested compounds against the M. tuberculosis multidrug-resistant strain MS-115 (MIC90 5 μg/mL).
- Matyugina, Elena,Novikov, Mikhail,Babkov, Denis,Ozerov, Alexander,Chernousova, Larisa,Andreevskaya, Sofia,Smirnova, Tatiana,Karpenko, Inna,Chizhov, Alexander,Murthu, Pravin,Lutz, Stefan,Kochetkov, Sergei,Seley-Radtke, Katherine L.,Khandazhinskaya, Anastasia L.
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p. 1387 - 1396
(2016/02/05)
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- Synthesis of substituted uracils by the reactions of halouracils with selenium, sulfur, oxygen and nitrogen nucleophiles under focused microwave irradiation
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Under microwave irradiation, the nucleophilic substitution reactions of halouracils with selenium, sulfur, oxygen and nitrogen nucleophiles was complete within several minutes with yields up to 99%. The method using microwave irradiation is superior to th
- Fang, Woei-Ping,Cheng, Yuh-Tsyr,Cheng, Yann-Ru,Cherng, Yie-Jia
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p. 3107 - 3113
(2007/10/03)
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- Synthesis of 5-(arylamino)-1-benzyluracils
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The synthesis of novel 5-(phenylamino)-, 5-(benzylamino)-, and 5-(phenethylamino) derivatives of 1-benzyluracil-containing different substituents in the aromatic nucleus has been carried out. Using the Hilbert-Johnson reaction it was found that N(1)
- Novikov,Ozerov
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p. 766 - 770
(2007/10/03)
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- INDAZOLINONE COMPOSITIONS USEFUL AS KINASE INHIBITORS
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The present invention provides compounds of formula (I): These compounds, and pharmaceutically acceptable compositions thereof, are useful generally as kinase inhibitors, particularly as inhibitors of PRAK, GSK3, ERK2, CDK2, MK2, SRC, SYK, and Aurora-2. Accordingly, compounds and compositions of the invention are useful for treating or lessening the severity of a variety of disorders, including, but not limited to, heart disease, diabetes, Alzheimer's disease, immunodeficiency disorders, inflammatory diseases, allergic diseases, autoimmune diseases, destructive bone disorders such as osteoporosis, proliferative disorders, infectious diseases and viral diseases.
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Page 197-198
(2008/06/13)
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- Synthesis of 1-(aryloxyalkyl)-5-(arylamino)uracils
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In an attempt to obtain new non-nucleoside inhibitors of the reverse transcriptase HIV-1, we have carried out the synthesis of 1-(benzyloxymethyl)- and 1-[2-(4-R-phenoxy)ethyl]-5-(arylamino)uracils. Indirect alkylation of trimethylsilyl derivatives of 5-(arylamino)uracils with benzyl chloromethyl ether by the Gilbert-Jones method did not affect the exocyclic amino group and gave the corresponding 1-(benzyloxymethyl) derivatives in 58-74% yield. Alkylation of 5-(arylamino)uracils with 1-bromo-2-(4-R-phenoxy)ethane in anhydrous DMF in the presence of potassium carbonate gave a mixture of N1-mono- and N1,N1-disubstituted products with an overall yield of 46-55%. 1998 Plenum Publishing Corporation.
- Ozerov,Novikov,Brel',Solodunova
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p. 611 - 616
(2007/10/03)
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