Morpholine, also known as Morphine and 1,4- Oxazacyclohexane. Morpholine has a wide range of industrial applications and can be used as an intermediate of many fine chemicals. Morpholine can be found in many fields such as rubber, medicine, pesticides, coatings, textiles, medical devices, etc. In the field of medicine, morpholine and its derivatives are mainly used to produce analgesic sedatives, local anesthetics, respiratory and vasodilator stimulants, body strengthening drugs, spasmolytic drugs and antimalarial drugs, such as morpholine gung, ibuprofen, naproxen, sodium phenylacetate, dichloroaniline, etc. Below, the manufacturer of N- methylmorpholine will introduce it to you!
A total of 268 morpholine drugs were recorded in the drug crossing database, among which 51 drugs were listed, mainly distributed in digestive system diseases, infectious diseases, tumors, cardiovascular and cerebrovascular diseases, respiratory system diseases and mental disorders. Morpholine is not only widely used in the field of diseases, but also not concentrated in the target point of view. Therefore, this paper mainly introduces some targets that have not been involved before.
1. muscarinic acetylcholine receptor family
Peptic ulcer occurs in the pylorus and duodenum of stomach, which is caused by the digestion of gastric juice. The occurrence of peptic ulcer is related to many factors, which can be divided into protective factors and injury factors. The former includes mucus, HCO3- and prostaglandin secreted by gastric mucus cells; The latter includes gastric acid, pepsin and Helicobacter pylori. Excessive secretion of gastric acid is the main cause of peptic ulcer, so the drugs that inhibit gastric acid secretion have become the means to resist peptic ulcer. These drugs can be divided into receptor antagonists and proton pump (H+/K+-ATPase) inhibitors. In the article "Application of benzimidazole in medicine", we mentioned proton pump inhibitor, which is more selective and has less side effects than histamine H2 receptor antagonist.
Among morpholine drugs, muscarinic acetylcholine receptor (mAChRs) antagonists, also known as M receptor antagonists, are used as anti-peptic ulcer drugs. In the process of gastric parietal cells secreting acid, M receptor, histamine H2 receptor and gastrin receptor all participate in it and play a promoting role. In addition, M receptor also participates in the processes of motor control, thermoregulation, cardiovascular regulation and memory in the central nervous system, and receives the regulation of smooth muscle contraction, gland secretion, heart rate and myocardial contractility in the peripheral nervous system. Therefore, the indications of M receptor antagonists also include smooth muscle spasm, anesthesia, nausea and vomiting, motion sickness and so on.
Proteasome is a multi-subunit macromolecular complex widely distributed in the cytoplasm and nucleus of eukaryotic cells, which has various catalytic functions and can selectively degrade intracellular proteins. Proteasome inhibitors affect the expression of cell growth-related proteins, cytokines and signal molecules by inhibiting the activity of proteasome, and interfere with the original process of cell proliferation, differentiation and apoptosis, and inhibit the growth of tumor cells more obviously.
Caffezomib, a morpholine drug developed by Onix Pharmaceuticals, was launched in 2012. It is used to treat multiple myeloma and is the second generation irreversible proteasome inhibitor . Compared with bortezomib, the first generation proteasome inhibitor, caffezomib has lower disease progression rate/mortality (36.9% vs. 52.3%), longer median progression-free survival time and more significant curative effect (unilateral p<0.001).
Third, polymerase acid protein
Polymerase acid protein is used to treat influenza A and B virus infection. Baloxavir marboxil is a new anti-influenza drug which is different from other antiviral drugs in the market. The drug is hydrolyzed into an active form against influenza virus, balosavir. It is an approved inhibitor of polymerase acid endonuclease, and balosavir aims to inhibit the endonuclease activity of polymerase acid (PA) protein, which is essential for influenza virus replication.