146557-83-7Relevant academic research and scientific papers
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.
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.
