Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1369311 | Bioorganic & Medicinal Chemistry Letters | 2014 | 4 Pages |
Abstract
A series of 2,3-disubstituted pyridines were synthesized as potential non-emetic PDE4 inhibitors. To decrease brain exposure and minimize emesis, we modified the lipophilic moiety of a series of emetic PDE4 inhibitors and found that introduction of a hydroxy group into the pyridine moiety of the side chain led to non-emetic compounds with preserved PDE4 inhibitory activity. Following optimization at the phenoxy group, we identified compound 1 as a potent non-emetic PDE4 inhibitor. Compound 1 showed significant efficacy in an animal model of asthma without inducing emesis.
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Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Motoji Kawasaki, Akira Fusano, Tomohiro Nigo, Shunya Nakamura, Mari N. Ito, Yasuhiro Teranishi, Satoshi Matsumoto, Hiroshi Toda, Naruaki Nomura, Takaaki Sumiyoshi,