124424-26-6Relevant articles and documents
S-ANTIGEN TRANSPORT INHIBITING OLIGONUCLEOTIDE POLYMERS AND METHODS
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, (2021/06/22)
Various embodiments provide STOPS? polymers that are S-antigen transport inhibiting oligonucleotide polymers, processes for making them and methods of using them to treat diseases and conditions. In some embodiments the STOPS? modified oligonucleotides include an at least partially phosphorothioated sequence of alternating A and C units having modifications as described herein. The sequence independent antiviral activity against hepatitis B of embodiments of STOPS? modified oligonucleotides, as determined by HBsAg Secretion Assay, is an EC50 that is less than 100 nM.
Mycobacterium tuberculosis thymidine monophosphate kinase inhibitors: Biological evaluation and conformational analysis of 2′- and 3′-modified thymidine analogues
Van Rompaey, Philippe,Nauwelaerts, Koen,Vanheusden, Veerle,Rozenski, Jef,Munier-Lehmann, Helene,Herdewijn, Piet,Van Calenbergh, Serge
, p. 2911 - 2918 (2007/10/03)
Mycobacterium tuberculosis thymidine monophosphate kinase (TMPKmt) has recently been introduced as a potential target for the structure-based design of anti-tuberculosis drugs. Based on the TMPKmt X-ray structure and previous S.A.R. studies, we synthesised the nucleoside analogues 3a-b, 6a-b, 7a-b, and 8a-b, modified in 2′- and 3′-position of the ribofuranose ring moiety. To our surprise, these analogues showed only moderate binding affinity (i.e. Ki between 118 and 1260 μM). This prompted us to investigate the conformational features of these nucleosides. We concluded that compounds of this series, especially 8a-b, are strongly biased towards the "Northern" furanose ring conformation, whereas X-ray crystallography reveals a preference of TMPKmt for the opposite "Southern" conformers. This paper covers the synthesis, biological evaluation and conformational features (i.e. preferred ring puckering) of the 2′- and 3′-modified dT analogues. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
Fluorinated sugar analogues of potential anti-HIV-1 nucleosides
Huang,Chen,Wang,Kim,Warshaw,Armstrong,Zhu,Chou,Watanabe,Matulic-Adamic,Su,Fox,Polsky,Baron,Gold,Hardy,Zuckerman
, p. 1640 - 1646 (2007/10/02)
In order to obtain agents with therapeutic indices superior to those of AZT, FLT, or D4T, several analogues of anti-HIV-1 nucleosides were synthesized. These include 2',3'-dideoxy-2',3'-difluoro-5-methyluridine (13), its arabino analogue 19, arabino-5-met
Synthesis and anti-HIV-1 activity of 2'-'up'-fluoro analogues of active anti-AIDS nucleosides 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxycytidine (DDC)
Watanabe,Harada,Zeidler,Matulic-Adamic,Takahashi,Ren,Cheng,Fox,Chou,Zhu,Polsky,Gold,Armstrong
, p. 2145 - 2150 (2007/10/02)
1-(3-Azido-2,3-dideoxy-2-fluoro-β-D-arabinofuranosyl)thymine (6, F-AZT) and 1-(2,3-dideoxy-2-fluoro-β-D-threopentofuranosyl)cytosine (12, F-DDC) were synthesized from the potent antiherpes virus nucleosides 1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)thymine
Synthesis and anti-HIV activity of several 2'-fluoro-containing pyrimidine nucleosides
Sterzycki,Ghazzouli,Brankovan,Martin,Mansuri
, p. 2150 - 2157 (2007/10/02)
Several 2'-fluoroarabino-2',3'-dideoxy- and 2'-fluoro-2',3'-unsaturated 2',3'-dideoxy pyrimidine nucleoside analogues are reported. The saturated analogues 1-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl)thymine (2'-threo-FddT, 33), 1-(2,3-dideoxy-2-fluoro-β-D-threo-pentofuranosyl)uracil (2'-threo-FddU, 22) were readily prepared from the corresponding 2'-deoxy-2'-fluoroarabinosyl nucleoside analogue by radical deoxygenation of the 3'-OH. The unsaturated compounds 1-(2,3-dideoxy-2-fluoro-β-D-glycero-pent-2-enofuranosyl)thymine (2'-Fd4T, 40) and 1-[5-O-(monomethoxytrityl)-2-fluoro-2,3-dideoxy-β-D-glycero -pent-2-enofuranosyl]uracil (39) were synthesized by an elimination reaction of the O-2,3'-anhydro-2'-fluoro-lyxo derivatives under basic conditions. The cytidine analogues 28 and 41 were prepared by amination of the corresponding uridine derivatives; compounds 28 and 41 were deprotected to give 1-(2,3-dideoxy-2-fluoro-β-D-arabinofuranosyl)cytidine (2'-threo-FddC, 29) and 1-(2,3-dideoxy-2-fluoro-β-D-glycero-pent-2-enofuranosyl)cytosine (2'-Fd4C, 42), respectively. All of these novel compounds were evaluated in vitro against human immunodeficiency virus (HIV) (LAV isolate). 2'-threo-FddC (29) was the most active of the newly synthesized substances against HIV with an ID50 of 0.8 μg/mL; ddC had an ID50 of 0.007 μg/mL. Because of its potency in the initial tests, 29 was further evaluated in both T cells and macrophage/monocyte cell lines, with several different isolates of HIV. Although 2'-threo-FddC (29) exhibited good antiviral activity in these systems, it was less active than AZT in these assays. At 1 μM the inhibition of CFU-GM by 29 was found to be 35-40%; this is slightly higher than seen with AZT.
SYNTHESIS OF 2',3'-DISUBSTITUTED 3'-DEOXYTHYMIDINE DERIVATIVES
Herdewijn, P.,Aerschot, A. Van
, p. 943 - 948 (2007/10/02)
Reaction of 2 with DAST followed by detritylation and monomethoxytritylation afforded 34percent of the fluorinated nucleoside 3.This intermediate was used to prepare the 3'-azido-2'-fluoro- and 2',3'-difluoro substituted 5-methyluridine analogues 7 and 11, respectively.
