Development of a novel sulfonate ester-based prodrug strategy

Kengo Hanaya, Shohei Yoshioka, Shinya Ariyasu, Shin Aoki, Mitsuru Shoji, Takeshi Sugai

研究成果: Article査読

9 被引用数 (Scopus)

抄録

A self-immolative γ-aminopropylsulfonate linker was investigated for use in the development of prodrugs that are reactive to various chemical or biological stimuli. To demonstrate their utility, a leucine-conjugated prodrug of 5-chloroquinolin-8-ol (5-Cl-8-HQ), which is a potent inhibitor against aminopeptidase from Aeromonas proteolytica (AAP), was synthesized. The sulfonate prodrug was considerably stable under physiological conditions, with only enzyme-mediated hydrolysis of leucine triggering the subsequent intramolecular cyclization to simultaneously release 5-Cl-8-HQ and form γ-sultam. It was also confirmed that this γ-aminopropylsulfonate linker was applicable for prodrugs of not only 8-HQ derivatives but also other drugs bearing a phenolic hydroxy group.

本文言語English
ページ(範囲)545-550
ページ数6
ジャーナルBioorganic and Medicinal Chemistry Letters
26
2
DOI
出版ステータスPublished - 2016 1 15

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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