Synthesis and in vitro stability of amino acid prodrugs of 6-β-naltrexol for microneedle-enhanced transdermal delivery

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:24

Article

Eldridge, Joshua A.^1,3  Milewski, Mikolaj¹  Stinchcomb, Audra L.^2,3  Crooks, Peter A.⁴ 

[1] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA

[2] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA

[3] AllTranz, Lexington, KY 40505 USA

[4] Univ Arkansas Med Sci, Coll Pharm, Dept Pharmaceut Sci, Little Rock, AR 72205 USA

关键词: Prodrugs;    Amino acid esters;    Microneedles;    Stability;    Transdermal;   

DOI  :  10.1016/j.bmcl.2014.09.072

来源: Elsevier

【 摘 要 】

A small library of amino acid ester prodrugs of 6-beta-naltrexol (NTXOL, 1) was prepared in order to investigate the candidacy of these prodrugs for microneedle-enhanced transdermal delivery. Six amino acid ester prodrugs were synthesized (6a-f). 6b, 6d, and 6e were stable enough at skin pH (pH 5.0) to move forward to studies in 50% human plasma. The lead compound (6e) exhibited the most rapid bioconversion to NTXOL in human plasma (t(1/2) = 2.2 +/- 0.1 h). (C) 2014 Elsevier Ltd. All rights reserved.

【 授权许可】

Free