Amino acid ester prodrugs of the thiazolides, introduced to improve the pharmacokinetic parameters of the parent drugs, proved to be stable as their salts but were unstable at pH > 5. Although some of the instability was due to simple hydrolysis, we have found that the main end products of the degradation were peptides formed by rearrangement. These peptides were stable solids: they maintained significant antiviral activity, and in general, they showed improved pharmacokinetics (better solubility and reduced clearance) compared to the parent thiazolides. We describe the preparation and evaluation of these peptides.

Stachulski, A.v., Rossignol, J., Pate, S., Taujanskas, J., Iggo, J.a., Aerts, R., et al. (2023). Thiazolide Prodrug Esters and Derived Peptides: Synthesis and Activity. ACS BIO & MED CHEM AU, 3(4), 327-334 [10.1021/acsbiomedchemau.2c00083].

Thiazolide Prodrug Esters and Derived Peptides: Synthesis and Activity

Piacentini, Sara;La Frazia, Simone;
2023-08-16

Abstract

Amino acid ester prodrugs of the thiazolides, introduced to improve the pharmacokinetic parameters of the parent drugs, proved to be stable as their salts but were unstable at pH > 5. Although some of the instability was due to simple hydrolysis, we have found that the main end products of the degradation were peptides formed by rearrangement. These peptides were stable solids: they maintained significant antiviral activity, and in general, they showed improved pharmacokinetics (better solubility and reduced clearance) compared to the parent thiazolides. We describe the preparation and evaluation of these peptides.
16-ago-2023
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/07
English
Senza Impact Factor ISI
antiviral
prodrug
time-course
NMR
rearrangement
influenza A
clinical
trials
Stachulski, A.v., Rossignol, J., Pate, S., Taujanskas, J., Iggo, J.a., Aerts, R., et al. (2023). Thiazolide Prodrug Esters and Derived Peptides: Synthesis and Activity. ACS BIO & MED CHEM AU, 3(4), 327-334 [10.1021/acsbiomedchemau.2c00083].
Stachulski, Av; Rossignol, J; Pate, S; Taujanskas, J; Iggo, Ja; Aerts, R; Pascal, E; Piacentini, S; La Frazia, S; Santoro, Mg; van Vooren, L; Sintubin...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/357023
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