146557-69-9Relevant academic research and scientific papers
Synthesis of carbon E, e -diene chain-linked dinucleotide analogues
Fargeas, Valérie,Ané, Adjou,Dubreuil, Didier,Lebreton, Jacques
scheme or table, p. 3341 - 3345 (2010/03/03)
The synthesis of a dinucleotide thymidine-thymidine linked by a carbon E,E-diene chain is described. This dimer is synthesized by a coupling reaction between an (E)-vinylstannane and an (E)-iodovinyl partner prepared from acetylenic parents, which are bot
Rational design of 5′-thiourea-substituted α-thymidine analogues as thymidine monophosphate kinase inhibitors capable of inhibiting mycobacterial growth
Van Daele, Ineke,Munier-Lehmann, Hélène,Froeyen, Matheus,Balzarini, Jan,Van Calenbergh, Serge
, p. 5281 - 5292 (2008/03/14)
Recently, thymidine monophosphate kinase (TMPK) emerged as an attractive target for developing inhibitors of Mycobacterium tuberculosis growth. The elucidation of the X-ray structure of TMPK of M. tuberculosis (TMPKmt), as well as the structure of an earlier serendipitously discovered dimeric thymidine inhibitor, laid the foundation for the design of potent and selective TMPKmt inhibitors reported here. Several hits identified within a series of 3′-C-branched thiourea-substituted β-thymidine derivatives inspired us to construct a set of 5′-thiourea-substituted α-thymidine derivatives characterized by a similar relative orientation of the thymine and arylthiourea moieties. α-Thymidine derivative 15, featuring a (3-trifluoromethyl-4-chlorophenyl)thiourea moiety, has a Ki of 0.6 μM and a selectivity index of 600 versus human TMPK. Moreover, it represents the first TMPK inhibitor showing good inhibitory activity on growing M. bovis (MIC99 = 20 μg/mL) and M. tuberculosis (MIC50 = 6.25 μg/mL) strains.
Synthesis of novel 3′-C-methylene thymidine and 5-methyluridine/cytidine H-phosphonates and phosphonamidites for new backbone modification of oligonucleotides
An,Wang,Maier,Manoharan,Ross,Cook
, p. 2789 - 2801 (2007/10/03)
Novel 5′-O-DMT- and MMT-protected 3′-C-methylene-modified thymidine, 5-methyluridine, and 5-methylcytidine H-phosphonates 1-7 with O-methyl, fluoro, hydrogen, and O-(2-methoxyethyl) substituents at the 2′-position have been synthesized by a new effective strategy from the corresponding key intermediates 3′-C-iodomethyl nucleosides and intermediate BTSP, prepared in situ through the Arbuzov reaction. The modified reaction conditions for the Arbuzov reaction prevented the loss of DMT- and MMT-protecting groups, and directly provided the desired 5′-O-DMT- and/or MMT-protected 3′-C-methylene-modified H-phosphonates 1-6 although some of them were also prepared through the manipulation of protecting groups after the P-C bond formation. The modified Arbuzov reaction of 3′-C-iodomethyl-5-methylcytidine 53, prepared from its 5-methyluridine derivative 42, with BTSP provided the 5-methylcytidine H-phosphonate 54, which was further transferred to the corresponding 4-N-(N- methylpyrrolidin-2-ylidene)-protected H-phosphonate monomer 7. 5′-O-MMT-protected 3′-C-methylene-modified H-phosphonates 5, 3, and 7 were converted to the corresponding cyanoethyl H-phosphonates 50, 51, and 56 using DCC as a coupling reagent. One-pot three-step reactions of 50, 51, and 56 provided the desired 3′-C-methylene-modified phosphonamidite monomers 8-10. Some of these new 3′-methylene-modified monomers 1-10 have been successfully utilized for the synthesis of 3′-methylene-modified oligonucleotides, which have shown superior antisense properties including nuclease resistance and binding affinity to the target RNA.
Modified oligonucleotides
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, (2008/06/13)
Novel compounds that mimic and/or modulate the activity of wild-type nucleic acids are provided. The novel compounds have modified internucleoside linkages which preferably replace naturally-occurring phosphodiester-5'-methylene linkages with four atom li
Backbone modified oligonucleotide analogs and preparation thereof through reductive coupling
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, (2008/06/13)
Methods for preparing oligonucleotide analogs which have improved nuclease resistance and improved cellular uptake are provided. In preferred embodiments, the methods involve reductive coupling of 3'- and 4'-substituted or 4'- and 3'-substituted nucleosid
Efficient and stereoselective synthesis of 3'-deoxy 3'-C-branched-chain substituted thymidine
Sanghvi,Bharadwaj,Debart,De Mesmaeker
, p. 1163 - 1166 (2007/10/02)
In this report, we provide for the first time a facile, efficient, and stereoselective synthesis of 1-[5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-3-C-formyl-β-D-erythro-p entofuranosyl]thymine (12), using an intermolecular radical C-C bond formation reacti
Comparison of two amides as backbone replacement of the phosphodiester linkage in oligodeoxynucleotides
Lebreton, Jacques,Waldner, Adrian,Fritsch, Valerie,Wolf, Romain M.,De Mesmaeker, Alain
, p. 5225 - 5228 (2007/10/02)
The two isomeric amide modifications 1 and 2 show similar effects on the melting temperature of RNA/DNA duplexes, when they replace the natural phosphodiester linkage in the DNA strand. The synthesis of the amide dimer 1 is presented.
