207278-99-7Relevant academic research and scientific papers
Naphthyridine derivatives
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, (2008/06/13)
PCT No. PCT/EP97/05898 Sec. 371 Date Apr. 27, 1999 Sec. 102(e) Date Apr. 27, 1999 PCT Filed Oct. 24, 1997 PCT Pub. No. WO98/18796 PCT Pub. Date May 7, 1998Novel 8-aryl-1,7-naphthyridines, in free or salt form, are PDE IV inhibitors and are thus useful as pharmaceuticals, e.g. for asthma therapy. Preferred compounds include compounds of formulae (I and II) wherein the R groups are as defined. Pharmaceutical compositions comprising the compounds, processes for preparation of the compounds and novel intermediates for use in the processes are disclosed.
Palladium-catalyzed cross-coupling reactions for the synthesis of 6,8- disubstituted 1,7-naphthyridines: A novel class of potent and selective phosphodiesterase type 4D inhibitors
Hersperger, Rene,Bray-French, Katharine,Mazzoni, Lazzaro,Müller, Thomas
, p. 675 - 682 (2007/10/03)
Recently, four subtypes of the human phosphodiesterase type 4 (PDE4A-D) enzyme have been described. So far, only very few PDE4 subtype-selective inhibitors are known. Herein, we describe the synthesis of 6,8-disubstituted 1,7-naphthyridines and their characterization as potent and selective inhibitors of PDE4D which suppress the oxidative burst in human eosinophils with IC50 values as low as 0.7 nM. SAR development and the extended use of palladium-catalyzed cross-coupling reactions led to compound 11 which inhibited human PDE4D with an IC50 value of 1 nM. Thus, compound 11 was 55, 175, and 1000 times more potent in inhibiting PDE4D over PDE4B, PDE4A, and PDE4C. In a Brown Norway rat model of allergic asthma, compound 11 when given by the oral route (1 mg/kg) reduced by more than 50% the influx of eosinophils, T-cells, and neutrophils into bronchoalveolar lavage fluid (BALF) samples obtained from antigen-challenged animals. Thus, PDE4D- selective inhibitors of the 1,7-naphthyridine class have the potential as an oral therapy for treating asthma.
