An Improved Procedure for the Synthesis of Nucleoside Phosphoramidates

2002 ◽  
Vol 6 (6) ◽  
pp. 819-822 ◽  
Author(s):  
Danielle M. Lehsten ◽  
David N. Baehr ◽  
Thomas J. Lobl ◽  
Andrew R. Vaino
Keyword(s):  
Nucleoside Phosphoramidates

Synthesis of Novel Dimeric Steroidal-Nucleoside Phosphoramidates.

ChemInform ◽  
2005 ◽  
Vol 36 (48) ◽  
Author(s):  
Sanhao Ji ◽  
Qiang Xiao ◽  
Yong Ju ◽  
Yufen Zhao
Keyword(s):  
Nucleoside Phosphoramidates

Synthesis of Novel Dimeric Steroidal-nucleoside Phosphoramidates

2005 ◽  
Vol 34 (7) ◽  
pp. 944-945 ◽  
Author(s):  
Sanhao Ji ◽  
Qiang Xiao ◽  
Yong Ju ◽  
Yufen Zhao
Keyword(s):  
Nucleoside Phosphoramidates

scholarly journals Synthesis and Anti-HIV Activity of some Novel Chain-Extended Phosphoramidate Derivatives of d4T (Stavudine): Esterase Hydrolysis as a Rapid Predictive Test for Antiviral Potency

1998 ◽  
Vol 9 (2) ◽  
pp. 109-115 ◽  
Author(s):  
C McGuigan ◽  
H-W Tsang ◽  
PW Sutton ◽  
E De Clercq ◽  
J Balzarini
Keyword(s):  
Human Immunodeficiency Virus ◽  
Selective Inhibitor ◽  
Amino Acid Derivatives ◽  
Predictive Test ◽  
Immunodeficiency Virus ◽  
Nucleoside Phosphoramidates ◽  
High Yields ◽  
Derivatives Of ◽  
Anti Hiv

Novel chain-extended nucleoside phosphoramidates of the anti-human immunodeficiency virus (HIV) drug d4T (stavudine) have been prepared as possible membrane-permeable prodrugs of the bio-active free 5′-monophosphates. Phosphorochloridate chemistry gave the target compounds in moderate to high yields, and all materials were fully characterized by spectroscopic and analytical methods. The compounds are related to the previously reported phenyl methoxyalaninyl derivative of d4T, which was shown to be a potent and selective inhibitor of HIV. In this study theamino acid nitrogen and ester moieties were separated by methylene spacers of between two and six carbon atoms. In vitro evaluation of these compounds indicated an almost complete lack of anti-HIV activity, the compounds being several orders of magnitude less potent than the corresponding α-amino acid derivatives. The reasons for the virtual lack of anti-HIV activity appear to involve poor enzyme-mediated hydrolysis.

scholarly journals Novel Nucleoside Phosphoramidates as Inhibitors of HIV: Studies on the Stereochemical Requirements of the Phosphoramidate Amino Acid

1996 ◽  
Vol 7 (4) ◽  
pp. 184-188 ◽  
Author(s):  
C. McGuigan ◽  
A. Salgado ◽  
C. Yarnold ◽  
T.Y. Harries ◽  
E. De Clercq ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Antiviral Activity ◽  
Antiviral Effect ◽  
Amino Acid Derivatives ◽  
Free Nucleotides ◽  
Nucleoside Phosphoramidates ◽  
Derivatives Of ◽  
Anti Hiv ◽  
Marked Dependence

Novel phosphoramidate derivatives of the anti-HIV nucleoside analogue d4T were designed to act as labile membrane-soluble prodrugs of the bio-active free nucleotide d4TMP. We herein reveal the very marked dependence of the antiviral activity of these phosphoramidates upon the stereochemistry of the amino acid attached to the phosphate centre; with a strong preference for the L-stereochemistry. These phosphate triesters were shown to liberate amino acid derivatives of the nucleotide intracellularly. These novel analogues, typified by alaninyl d4T monophosphate, may act as intracellular sources of the free nucleotides. The alaninyl d4T adducts themselves exert an antiviral effect when administered extracellularly, but again with clear distinctions between the L- and D-series. This evidence indicates that extracellularly administered blocked triesters derived from L-amino acids can generate d4TMP intracellularly, by a new pathway which is highly dependent on the amino acid stereochemistry.

A Novel Method for the Preparation of Nucleoside Triphosphates from Activated Nucleoside Phosphoramidates

2004 ◽  
Vol 6 (13) ◽  
pp. 2257-2260 ◽  
Author(s):  
Weidong Wu ◽  
Caren L. Freel Meyers ◽  
Richard F. Borch
Keyword(s):  
Nucleoside Triphosphates ◽  
Novel Method ◽  
Nucleoside Phosphoramidates

scholarly journals Influence of the Nucleobase and Anchimeric Assistance of the Carboxyl Acid Groups in the Hydrolysis of Amino Acid Nucleoside Phosphoramidates

2011 ◽  
Vol 18 (3) ◽  
pp. 857-868 ◽  
Author(s):  
Munmun Maiti ◽  
Servaas Michielssens ◽  
Natalia Dyubankova ◽  
Mohitosh Maiti ◽  
Eveline Lescrinier ◽  
...  
Keyword(s):  
Amino Acid ◽  
Anchimeric Assistance ◽  
Nucleoside Phosphoramidates ◽  
Hydrolysis Of

DMPK and Metabolism Studies of Nucleoside Phosphoramidates Including INX-08189, A Novel Double Pro-drug and Clinical Candidate for Hepatitis C Virus Therapy

2011 ◽  
Vol 90 (2) ◽  
pp. A22-A23 ◽  
Author(s):  
Jeff T. Hutchins ◽  
Christopher McGuigan ◽  
Stanley D. Chamberlain ◽  
Karolina W. Madela ◽  
Mohamed Aljarah ◽  
...  
Keyword(s):  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Nucleoside Phosphoramidates ◽  
Clinical Candidate

ChemInform Abstract: Hydrolytic Reactions of Nucleoside Phosphoramidates: Kinetics and Mechanisms

ChemInform ◽  
2010 ◽  
Vol 41 (26) ◽  
pp. no-no
Author(s):  
Tuomas Lonnberg ◽  
Mikko Ora ◽  
Harri Lonnberg
Keyword(s):  
Nucleoside Phosphoramidates

scholarly journals Reactivity of Amino Acid Nucleoside Phosphoramidates: A Mechanistic Quantum Chemical Study

2011 ◽  
Vol 116 (1) ◽  
pp. 644-652 ◽  
Author(s):  
Servaas Michielssens ◽  
Munmun Maiti ◽  
Mohitosh Maiti ◽  
Natalia Dyubankova ◽  
Piet Herdewijn ◽  
...  
Keyword(s):  
Amino Acid ◽  
Quantum Chemical ◽  
Quantum Chemical Study ◽  
Chemical Study ◽  
Nucleoside Phosphoramidates

scholarly journals Synthesis and antiproliferative evaluation of novel azido nucleosides and their phosphoramidate derivatives

2017 ◽  
Vol 89 (9) ◽  
pp. 1267-1281 ◽  
Author(s):  
Nuno M. Xavier ◽  
Rita Gonçalves-Pereira ◽  
Radek Jorda ◽  
Eva Řezníčková ◽  
Vladimír Kryštof ◽  
...  
Keyword(s):  
Cell Lines ◽  
Leukemia Cell ◽  
K562 Cells ◽  
Leukemia Cell Line ◽  
Bt474 Cell ◽  
Purine Derivative ◽  
Antiproliferative Effects ◽  
Nucleoside Phosphoramidates ◽  
Myeloid Leukemia Cell ◽  
Mcf 7

Abstract:New xylofuranosyl and glucopyranosyl nucleoside phosphoramidates were synthesized as potential mimetics of nucleoside 5′-monophosphates. Their access involved N-glycosylation of uracil and 2-acetamido-6-chloropurine with 5′/6′-azido-1,2-di-O-acetyl glycosyl donors and subsequent Staudinger-phosphite reaction of the resulting azido nucleosides. The coupling of the purine derivative with the pyranosyl donor furnished N9- and N7-linked nucleosides in 1:1 ratio, whereas with the furanosyl donor, the N9-nucleoside was the major regioisomer formed. When using uracil, only 5′/6′-azido N1-linked nucleosides were obtained. The purine 5′/6′-azido nucleosides were converted into corresponding phosphoramidates in good yields. The antiproliferative effects of the nucleoside phosphoramidates and those of the azido counterparts on cancer cells were evaluated. While the nucleoside phosphoramidates did not show significant activities, the purine 5′/6′-azido nucleosides displayed potent effects against K562, MCF-7 and BT474 cell lines. The 5′-azidofuranosyl N9 and N7-linked purine nucleosides exhibited highest activity towards the chronic myeloid leukemia cell line (K562) with GI50 values of 13.6 and 9.7 μM, respectively. Among pyranosyl nucleosides, the N7-linked nucleoside was the most active compound with efficacy towards all cell lines assayed and a highest effect on K562 cells (GI50=6.8 μM). Cell cycle analysis of K562 and MCF-7 cells showed that the most active compounds cause G2/M arrest.

Sign in / Sign up

Export Citation Format

Share Document