Synthesis And Research Of Benzyl Pyridine Derivatives

Acetylcholine receptors on the parasympathetic ganglia postganglionic fibre is sensitive to muscarine,they are called muscarinic acetylcholine receptor(M receptor). M receptor belong to G-protein coupled receptor family, it have five subtypes: M1, M2, M3, M4 and M5. M receptor can regulate smooth muscle contraction and some nervous system function.In the peripheral nervous system,M3 receptor is most distributed in bladder, respiratory passages and gastrointestinal system, and M3 receptor is concerned with OAB, COPD, IBS. Benzyl pyridine derivatives are important intermediate of synthesis selective M3 receptor antagonists. The objective of this research is to design and synthesis various kinds of benzyl pyridine derivatives, by screening them, to get active compounds which have independent intellectual property rights. By researching the selected compounds, expect to find novel OAB drugs. Achievement of this research is as follows:1 Summarized the structure of drugs on sale and compounds at different clinical stage, with considering of feasibility and creativity, we designed a series of compounds, whose hydrophobic regions are one pyridine and one substituted phenyl, hydrogen bonding receptor is hydroxy, and basic core is 3-quinuclidinol.2 Analyzed the retrosynthesis route of this compounds, and with considering of the cost of materials, the feasibility and safety of every reaction, designed reasonable synthetic route for every compound.3 Start from picolinic acid, by using Friedel-crafts reaction, Reformatsky reaction and so on, total synthesised every compound according to their synthetic route. The synthesized compounds were confirmed by 1HNMR.