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 language | English |
|---|---|
| Pages (from-to) | 1323-1327 |
| Number of pages | 5 |
| Journal | Bioorganic and Medicinal Chemistry Letters |
| Volume | 14 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2004 Mar 8 |
| Externally published | Yes |
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