Orally active PDE4 inhibitors with therapeutic potential

Hiroshi Ochiai, Tazumi Ohtani, Akiharu Ishida, Katuya Kishikawa, Takaaki Obata, Hisao Nakai, Masaaki Toda

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Based on the successful results in the clinical trial of Ariflo™, further optimization of the spatial arrangement of the three pharmacophores (carboxylic acid moiety, nitrile moiety and 3-cyclopentyl-4-methoxyphenyl moiety) in the structure of Ariflo 1 was attempted using a bicyclo[3· 3·0]octane template instead of a cyclohexane template. As a result, 2a, 7a and 7b were found to be orally active and were predicted to have an improved therapeutic potential based on evaluation by cross-species and same-species comparisons. Structure-activity relationships (SARs) of these compounds are also discussed.

Original languageEnglish
Pages (from-to)1323-1327
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume14
Issue number5
DOIs
Publication statusPublished - 2004 Mar 8
Externally publishedYes

Keywords

  • Bicyclo[3·3·0]octane
  • Orally active
  • PDE4 inhibitor
  • Three pharmacophores

ASJC Scopus subject areas

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

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  • Cite this

    Ochiai, H., Ohtani, T., Ishida, A., Kishikawa, K., Obata, T., Nakai, H., & Toda, M. (2004). Orally active PDE4 inhibitors with therapeutic potential. Bioorganic and Medicinal Chemistry Letters, 14(5), 1323-1327. https://doi.org/10.1016/j.bmcl.2003.12.018