1992
DOI: 10.1177/095632029200300302
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5′Prime;-Ester Prodrugs of the Varicella-Zoster Antiviral Agent, 6-Methoxypurine Arabinoside

Abstract: SummaryThe potent and selective activity of 6-methoxypurine arabinoside (9B[I3-D-arabinofuranosyl]-6-methoxy-9H-purine; 1) and its pharmacokinetic limitations have been described previously. In an attempt to circumvent first-pass catabolism following oral administration, a series of 5 ' -esters (2a-t) was prepared by dicyclohexyl-carbodiimide-promoted condensation with formic acid in the case of 2a, or by direct acylation of the parent nucleoside with the corresponding acyl chloride. These compounds were evalu… Show more

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Cited by 15 publications
(4 citation statements)
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“…A potential route of nonproductive metabolism during absorption is metabolism of the adenosine-like C -nucleobase by the action of adenosine deaminase that is highly expressed in intestinal mucosa. Indeed, ester prodrugs of adenosine analogs have been previously designed to potentially alleviate adenosine deaminase metabolism during absorption. , The metabolism of 2 and 3 by adenosine deaminase was therefore investigated in vitro, and both compounds were found to be weak substrates or inhibitors of adenosine deaminase (see Supporting Information). The in vitro data suggests that the oral bioavailability of 2 may not be significantly impacted by undesired intestinal metabolism.…”
Section: Resultsmentioning
confidence: 99%
“…A potential route of nonproductive metabolism during absorption is metabolism of the adenosine-like C -nucleobase by the action of adenosine deaminase that is highly expressed in intestinal mucosa. Indeed, ester prodrugs of adenosine analogs have been previously designed to potentially alleviate adenosine deaminase metabolism during absorption. , The metabolism of 2 and 3 by adenosine deaminase was therefore investigated in vitro, and both compounds were found to be weak substrates or inhibitors of adenosine deaminase (see Supporting Information). The in vitro data suggests that the oral bioavailability of 2 may not be significantly impacted by undesired intestinal metabolism.…”
Section: Resultsmentioning
confidence: 99%
“…Indeed, ester prodrugs of adenosine analogs have been previously designed to potentially alleviate adenosine deaminase metabolism during absorption. [36][37] The metabolism of 2 and 3 by adenosine deaminase was therefore investigated in vitro and both compounds were found to be weak substrates or inhibitors of adenosine deaminase (see supporting information). The in-vitro data suggests that the oral bioavailability of 2 may not be significantly impacted by undesired intestinal metabolism.…”
Section: Resultsmentioning
confidence: 99%
“…In turn, derivatization of antipsychotic haloperidol by means of fatty acids of different aliphatic chain lengths (up to decanoate ester) furnished excellent prodrugs with sustained release and significantly prolonged duration of action [42]. Finally, anti-cancer drug gemcitabine esterified with various aliphatic amino acids yielded prodrugs with high affinity for the PEPT1 transporter [43], whereas a powerful anti-leukemic agent, namely 9-β-D-arabinofuranosyl guanine (ara-G), acetylated regioselectively at 5 -position rendered derivative of significantly improved solubility and bioavailability [44,45]. Other examples of prodrug strategies for cancer cell-specific targeting, extensively utilized in oncotherapies, can be found in recent review articles [46,47].…”
Section: Introductionmentioning
confidence: 99%