68724-11-8Relevant articles and documents
Synthesis and antiviral activities of new acyclic and "double-headed" nucleoside analogues
Zhang, Xinying,Amer, Adel,Fan, Xuesen,Balzarini, Jan,Neyts, Johan,De Clercq, Erik,Prichard, Mark,Kern, Earl,Torrence, Paul F.
, p. 221 - 232 (2007)
To develop an understanding of the structure-activity relationships for the inhibition of orthopoxviruses by nucleoside analogues, a variety of novel chemical entities were synthesized. These included a series of pyrimidine 5-hypermodified acyclic nucleoside analogues based upon recently discovered new leads, and some previously unknown "double-headed" or "abbreviated" nucleosides. None of the synthetic products possessed significant activity against two representative orthopoxviruses; namely, vaccinia virus and cowpox virus. They were also devoid of significant activity against a battery of other DNA and RNA viruses. So far as the results with the orthopoxviruses and herpes viruses, the results may point to the necessity for nucleoside analogues 5′-phosphorylation for antiviral efficacy.
Potentiation of the antitumor effect of 5-fluoro-2'-deoxyuridine esters in combination with acyclothymidine esters on L1210 in mice via oral administration
Kawaguchi,Saito,Saneyoshi
, p. 939 - 943 (1988)
Fifteen pyrimidine-related compounds were evaluated for their ability to inhibit enzymatic degradation of 5-fluoro-2'-deoxyuridine (FUdR). Acyclothymidine [5-methyl-1-(2'-hydroxyethoxymethyl)uracil] showed the highest inhibitory effect on the phosphorolytic degradation of FUdR in various tissue homogenates derived from mouse, rat, and beagle organs. Both the drug (FUdR) and the inhibitor (acyclothymidine) were esterified with appropriate aliphatic acids in order to synchronize their behavior after simultaneous oral administration. The antitumor activity of orally administered FUdR esters was potentiated by the simultaneous oral administration of the acyclothymidine esters, but not by acyclothymidine.
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.
