Morpholine contains secondary amine groups and has all the typical reactive characteristics of secondary amine groups. It can react with inorganic acids to form salts, and react with organic acids to form salts or amides, which can be subjected to alkylation reaction, and can also be reacted with ethylene oxide, ketone or Willgerodt reaction. Morpholine is a six-membered ring containing oxygen and nitrogen, and its alkalinity is much lower than that of its parent piperidine. The marketed morpholine drugs are mainly distributed in the fields of tumors, cardiovascular and cerebrovascular diseases, respiratory system diseases, digestive system diseases, infectious diseases and mental disorders.
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A spiro compound is a polycyclic compound in which two monocyclic rings share one carbon atom; the shared carbon atom is called a spiro atom. Spiro compounds have rigid structures, stable structures, and have special properties that general organic compounds do not possess, such as anomeric effect, spiro conjugation and spiro hyperconjugation. Compared with the monocyclic structure or the planar aromatic structure, the spiro structure has a larger three-dimensional structure; the heterocyclic spiro structure is also regarded as the biological isostere of some groups, which can change the drug to a certain extent. The water solubility, lipophilicity, dominant conformation and ADMET properties of the molecule make the optimized lead molecule easier to drug. Therefore, spiro compounds occupy a very important position in drug development.
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Azetidines are an important class of saturated four-membered nitrogen-containing heterocyclic compounds. The research hotspots related to this structure mainly focus on two aspects: one is the research of pharmaceutical chemistry; the other is related to chiral azetidines, using rigid azetidine compounds as chiral ligands for asymmetric catalytic reactions. Many nitrogen-containing heterocycles play important roles in drug structures, and in many cases small structural changes can improve ligand selectivity and pharmacokinetic properties.
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