644986-06-1Relevant academic research and scientific papers
Identification of 2,3-disubstituted pyridines as potent, non-emetic PDE4 inhibitors
Kawasaki, Motoji,Fusano, Akira,Nigo, Tomohiro,Nakamura, Shunya,Ito, Mari N.,Teranishi, Yasuhiro,Matsumoto, Satoshi,Toda, Hiroshi,Nomura, Naruaki,Sumiyoshi, Takaaki
, p. 2689 - 2692 (2014/06/09)
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.
