Overall Synthesis of GSK356278: Quick Delivery of a PDE4 Inhibitor Using a Fit-for-Purpose Approach was written by Guercio, Giuseppe;Castoldi, Damiano;Giubellina, Nicola;Lamonica, Alessandro;Ribecai, Arianna;Stabile, Paolo;Westerduin, Pieter;Dams, Riet;Nicoletti, Anna;Rossi, Sara;Bismara, Claudio;Provera, Stefano;Turco, Lucilla. And the article was included in Organic Process Research & Development in 2010.Computed Properties of C5H9N3 This article mentions the following:
The family of phosphodiesterase (PDE) enzymes hydrolyze cyclic nucleotides, cAMP and cGMP, leading to their inactivation as intracellular second messengers. Inhibition of these enzymes leads to an elevation of levels of cyclic nucleotides in the cell and prolongs their action on downstream signaling pathways. PDE4, of which there are four subtypes, is widely expressed throughout the brain but is also abundant in the periphery in inflammatory and immune cells, in the gastrointestinal tract, and in cardiac myocytes. GSK356278 (I) is a potent, selective, and competitive inhibitor of PDE4 enzymes currently under investigation for the treatment of CNS disorders. The initial synthetic route developed by Medicinal Chem. Department, used several hazardous and/or expensive reagents and harsh conditions and gave relatively low yields. By targeted process of research and development plus application of anal. techniques to identify byproduct and extensive route scouting, a novel synthetic route for I has been developed. This contribution reports the optimization of the chem. synthesis of I to develop a large-scale process suitable for its synthesis. In the experiment, the researchers used many compounds, for example, 1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3Computed Properties of C5H9N3).
1-Ethyl-1H-pyrazol-5-amine (cas: 3528-58-3) belongs to pyrazole derivatives. As is the case with imidazoles, the pyrazole ring offers many opportunities to create new multiring systems that incorporate this heterocycle. Protonation of pyrazole in strong acid leads to pyrazolium cations, which undergo electrophilic substitution preferentially at C3 rather than C4. The pyrazole anion is not reactive toward nucleophiles but is mostly reactive to electrophiles.Computed Properties of C5H9N3
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics