1345014-22-3

Upstream product

• 2142-63-4 1-(3-Bromophenyl)ethanone 
• 1345014-07-4 tert-Butyl 2-(3-bromophenyl)-4-(methylsulfonyl)-5-oxo-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate 
• 1345013-96-8 tert-Butyl 2-(3-bromophenyl)-4-(methylthio)-5-oxo-7,8-dihydro-1,6-naphthyridine-6(5H)-carboxylate 
• 1345013-92-4 tert-butyl 3-[bis(methylthio)methylene]-2,4-dioxopiperidine-1-carboxylate 

Downstream Products

• 1345014-24-5 4-amino-2-(3-bromophenyl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one 
• 1345014-25-6 4-Amino-2-(3'-hydroxybiphenyl-3-yl)-7,8-dihydro-1,6-naphthyridin-5(6H)-one 

Relevant academic research and scientific papers

4-Amino-7,8-dihydro-1,6-naphthyridin-5(6 H)-ones as Inhaled Phosphodiesterase Type 4 (PDE4) Inhibitors: Structural Biology and Structure-Activity Relationships

Rational design of a novel template of naphthyridinones rapidly led to PDE4 inhibitors with subnanomolar enzymatic potencies. X-ray crystallography confirmed the binding mode of this novel template. We achieved compounds with double-digit picomolar enzymatic potencies through further structure-based design by targeting both the PDE4 enzyme metal-binding pocket and occupying the solvent-filled pocket. A strategy for lung retention and long duration of action based on low aqueous solubility was followed. In vivo efficacies were measured in a rat lung neutrophilia model by suspension microspray and dry powder administration. Suspension microspray of potent compounds showed in vivo efficacy with a clear dose-response. Despite sustained lung levels, dry powder administration performed much less well and without proper dose-response, highlighting clear differences between the two formulations. This indicates a deficiency in the low aqueous solubility strategy for long duration lung efficacy.

A modular synthesis of novel 4-amino-7,8-dihydro-1,6-naphthyridin-5(6H)- ones as PDE4 inhibitors

A versatile, modular synthetic route to a series of 4-amino-7,8-dihydro-1, 6-naphthyridin-5(6H)-ones has been developed. These compounds represent a novel structural class of potent phosphodiesterase IV (PDE4) inhibitors.

New 7,8-dihydro-1,6-naphthyridin-5(6h)-one-derivatives as PDE4 inhibitors

New 7,8-dihydro-1,6-naphthyridin-5(6H)-one derivatives derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of the phosphodiesterase IV (PDE4).