263390-44-9Relevant articles and documents
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
supporting information, 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.
2,3-disubstituted pyridine derivatives, process for the preparation thereof, drug compositions containing the same and intermediates for the preparation
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, (2008/06/13)
A compound of the formula (I) wherein A is O, S, CHR1or NR2, R1and R2are H, lower alkyl, X1and X2are H, halogen, nitro, cyano, etc., Y1is H, lower alkyl, Z1and Z2are H, halogen, cyano, hydroxy, lower alkyl, etc., and n is an integer of 2 to 4, a pharmaceutically acceptable salt thereof, a process for preparing the same, a pharmaceutical composition containing the same as an active ingredient, and an intermediate therefor. The compounds (I) of the present invention show a potent PDE IV inhibitory activity as well as an excellent bronchodilating activity, and hence, they are widely useful as a PDE IV inhibitor in the treatment or prophylaxis of allergic inflammatory diseases or organ inflammatory diseases, especially in the treatment or prophylaxis of pulmonary diseases accompanied by airway obstruction such as asthma.
