Prodrugs of nucleoside analogues for improved oral absorption and tissue targeting

Li, Fujun; Maag, Hans; Alfredson, Tom

doi:10.1002/jps.21047

Cited by 139 publications

(118 citation statements)

References 165 publications

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“…This is considered to be the reason for the greater bioavailability of valacyclovir than acyclovir (Soul-Lawton et al, 1995). The recognition of various types of therapeutic agents by PEPT1 has led to use of this transporter in rational drug design (Li et al, 2008;Brandsch, 2009). However, it is also important to consider influx transporter-mediated drug interactions (Banfield et al, 2002;Lilja et al, 2005a,b).…”

Section: Introductionmentioning

confidence: 99%

Functional Expression of Carnitine/Organic Cation Transporter OCTN1/SLC22A4 in Mouse Small Intestine and Liver

et al. 2010

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ABSTRACT:Carnitine/organic cation transporter (OCTN1/SLC22A4) accepts various therapeutic agents as substrates in vitro and is expressed ubiquitously, although its function in most organs has not yet been examined. The purpose of the present study was to evaluate functional expression of OCTN1 in small intestine and liver, using octn1 gene knockout [octn1(؊/؊)] mice. After oral administration of [

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Section: Introductionmentioning

confidence: 99%

Functional Expression of Carnitine/Organic Cation Transporter OCTN1/SLC22A4 in Mouse Small Intestine and Liver

et al. 2010

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“…Following oral administration of valganciclovir in human, the absolute bioavailability of ganciclovir could be 10-fold higher than that from oral ganciclovir (Jung & Dorr, 1999;Pescovitz et al, 2000). According to these studies, no significant amount of the prodrug was detected in plasma which may be indicative of rapid and complete hydrolysis of valganciclovir to ganciclovir in vivo (Li et al, 2008). Conversion of valganciclovir to ganciclovir is a hydrolytic reaction and therefore is not dependent to molybdenum hydroxylases.…”

Section: Ganciclovirmentioning

confidence: 90%

“…Many nucleoside analogues have antiviral and antitumor properties. During the last decades, numerous nucleoside analogues and their prodrugs were developed for cancer chemotherapy, treatment of patients with infections of human immunodeficiency virus (HIV) and infections caused by herpes and hepatitis viruses (Li et al, 2008). In spite of having excellent pharmacological activity, they often suffer from a poor oral bioavailability due to low intestinal absorption.…”

Section: Biological and Pharmacological Importance Of Purinesmentioning

confidence: 99%

“…In spite of having excellent pharmacological activity, they often suffer from a poor oral bioavailability due to low intestinal absorption. Therefore, intense research efforts have been focused on developing nucleoside analogues prodrugs, mainly in the acyclic form, to improve oral absorption (Li et al, 2008).…”

Section: Biological and Pharmacological Importance Of Purinesmentioning

confidence: 99%

“…The first step, oxidation of the 6-aminopurine moiety to guanine, is mediated by XO (Winkler et al, 1990). However, no further studies of HOE 602 have been published (Li et al, 2008). (Winkler et al, 1990).…”

Section: Ganciclovirmentioning

confidence: 99%

See 2 more Smart Citations

Role of Aldehyde Oxidase and Xanthine Oxidase in the Metabolism of Purine-Related Drugs

Rashidi¹,

Pashaei-Asl²

2012

Readings in Advanced Pharmacokinetics - Theory, Methods and Applications

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Symmetrical Diamidate Prodrugs of Nucleotide Analogues for Drug Delivery

Pertusati

McGuigan

Serpi

2015

CP Nucleic Acid Chemistry

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The use of pronucleotides to circumvent the well-known drawbacks of nucleotide analogs has played a significant role in the area of antiviral and anticancer drug delivery. Several motifs have been designed to mask the negative charges on the phosphorus moiety of either nucleoside monophosphates or nucleoside phosphonates, in order to increase their hydrophobicity and allow entry of the compound into the cell. Among them the bis-amidate analogs, having two identical amino acids as masking groups through a P-N bond, represent a more recent approach for the delivery of nucleotide analogs, endowed with antiviral or anticancer activity. Different synthetic strategies are commonly used for preparing phosphorodiamidates of nucleosides. In this protocol, we would like to focus on the description of the synthetic methodology that in our hand gave the best results using 2'-3'-didehydro-2'-3'-dideoxythymidine (d4T, Stavudine) as model nucleoside. A second strategy for preparing diamidates of nucleoside phosphonates will be reported using {[2-(6-amino-9 H-purin-9-yl)ethoxy]methyl}phosphonic acid (PMEA, adefovir) as model substrate.

show abstract

Prodrugs of nucleoside analogues for improved oral absorption and tissue targeting

Cited by 139 publications

References 165 publications

Functional Expression of Carnitine/Organic Cation Transporter OCTN1/SLC22A4 in Mouse Small Intestine and Liver

Functional Expression of Carnitine/Organic Cation Transporter OCTN1/SLC22A4 in Mouse Small Intestine and Liver

Role of Aldehyde Oxidase and Xanthine Oxidase in the Metabolism of Purine-Related Drugs

Symmetrical Diamidate Prodrugs of Nucleotide Analogues for Drug Delivery

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