Biphenyl Pyridazinone Derivatives as Inhaled PDE4 Inhibitors: Structural Biology and Structure-Activity Relationships was written by Gracia, Jordi;Buil, Maria Antonia;Castro, Jordi;Eichhorn, Peter;Ferrer, Manel;Gavalda, Amadeu;Hernandez, Begona;Segarra, Victor;Lehner, Martin D.;Moreno, Imma;Pages, Lluis;Roberts, Richard S.;Serrat, Jordi;Sevilla, Sara;Taltavull, Joan;Andres, Miriam;Cabedo, Judit;Vilella, Dolors;Calama, Elena;Carcasona, Carla;Miralpeix, Montserrat. And the article was included in Journal of Medicinal Chemistry in 2016.Electric Literature of C8H6BrFO2 This article mentions the following:
Cyclic nucleotide cAMP is an ubiquitous second messenger involved in a plethora of cellular responses to biol. agents involving activation of adenylyl cyclase. Its intracellular levels are tightly controlled by a family of cyclic nucleotide degrading enzymes, the PDEs. In recent years, cyclic nucleotide phosphodiesterase type 4 (PDE4) has aroused scientific attention as a suitable target for anti-inflammatory therapy in respiratory diseases, particularly in the management of asthma and COPD. Here the authors describe efforts to discover novel, highly potent inhaled inhibitors of PDE4. Through structure based design, with the intervention of a wide variety of functional groups and physichochem. profiles to occupy the solvent-filled pocket of the PDE4 enzyme, the authors modified the structure of the authors’ oral PDE4 inhibitors to reach compounds up to picomolar enzymic potencies. In vitro potencies were demonstrated in a rat lung neutrophilia model by suspension microspray administration. In the experiment, the researchers used many compounds, for example, Methyl 3-bromo-4-fluorobenzoate (cas: 82702-31-6Electric Literature of C8H6BrFO2).
Methyl 3-bromo-4-fluorobenzoate (cas: 82702-31-6) belongs to organobromine compounds. Bromine is more electronegative than carbon (2.9 vs 2.5). Consequently, the carbon in a carbon–bromine bond is electrophilic, i.e. alkyl bromides are alkylating agents. The principal reactions for organobromides include dehydrobromination, Grignard reactions, reductive coupling, and nucleophilic substitution.Electric Literature of C8H6BrFO2
Referemce:
Bromide – Wikipedia,
bromide – Wiktionary