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 was written by Hersperger, Rene;Bray-French, Katharine;Mazzoni, Lazzaro;Mueller, Thomas. And the article was included in Journal of Medicinal Chemistry in 2000.Recommanded Product: 5912-35-6 This article mentions the following:
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 a compound which inhibited human PDE4D with an IC50 value of 1 nM. Thus, the compound 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, the compound 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. In the experiment, the researchers used many compounds, for example, 6-Amino-8-bromo-1,7-naphthyridine (cas: 5912-35-6Recommanded Product: 5912-35-6).
6-Amino-8-bromo-1,7-naphthyridine (cas: 5912-35-6) belongs to naphthyridine derivatives. Heterocyclic nitrogen compounds, including fused 1,5-naphthyridines, have versatile applications in synthetic organic chemistry and play an important role in the field of medicinal chemistry, as many of them have a wide range of biological activities. Transition metal complexes of 1,5-naphthyridine (1,5-napy) seems to form one-dimensional coordination polymers with the ligand acting as bidentate in a “stepped” bridging fashion.Recommanded Product: 5912-35-6
Referemce:
1,8-Naphthyridine – Wikipedia,
1,8-Naphthyridine | C8H6N2 – PubChem