Tropisetron hydrochloride(link:https://www.bloomtechz.com/synthetic-chemical/api-researching-only/tropisetron-hydrochloride-cas-105826-92-4.html) is a commonly used 5-HT3 receptor antagonist, which is mainly used to prevent and treat nausea and vomiting caused by chemotherapy and radiotherapy. It belongs to the indole alkaloids and has a high affinity with 5-HT3 receptors. There are many ways to prepare Tropisetron hydrochloride. I will list one of the most common methods for description, but it should be noted that this method is only a brief description. If you need a detailed method, please send an email to Shaanxi Achieve chem-tech Co.,Lt .
Tropisetron Hydrochloride Synthesis
Indole‑2‑carbonyl chloride reacts with proline to generate Tropisetron hydrochloride. The following are the detailed steps for preparing Tropisetron hydrochloride:
1. Dissolve indole-2-formyl chloride in an appropriate amount of DMF to form solution A.
2. Dissolve proline in an appropriate amount of N-methylpyrrolidone to form solution B.
3. Mix solution A and solution B at room temperature and stir well.
4. Add appropriate amount of potassium carbonate to keep the reaction system alkaline.
5. Under the protection of nitrogen, the reaction system was heated to 80° C. and kept at a constant temperature for 12 hours.
6. After the reaction, cool to room temperature. Add an appropriate amount of anhydrous magnesium sulfate, and dry the reaction system.
7. Remove magnesium sulfate by filtration to obtain a crude product.
purification:
1. Dissolve the crude product in an appropriate amount of hydrochloric acid to form solution C.
2. Adjust the pH value of solution C to about 7.5 with ammonia water to free the product.
3. Remove insolubles by filtration to obtain free indole-2-formyl chloride.
Crystallization and drying:
1. Dissolve free indole-2-formyl chloride in an appropriate amount of ethanol to form solution D.
2. Add an appropriate amount of hydrogen chloride to solution D, and adjust the pH value to about 5.5.
3. Crystallization solution D to obtain Tropisetron hydrochloride crystals.
4. Filter the crystals and dry to obtain the final product.
The reactions involved in the above steps are as follows:
1. Indole-2-formyl chloride reacts with proline to generate Tropisetron hydrochloride:
COCl2 + NH(CH2CH2NH)CH(CH3)CH(CH3) → NH(CH2CH2NH)CH(CH3)CH(CH3) + HCl + CO2
2. Add potassium carbonate to keep the reaction system alkaline:
COCl2 + NH(CH2CH2NH)CH(CH3)CH(CH3) → NH(CH2CH2NH)CH(CH3)CH(CH3) + NH4Cl + CO2
3. Adjust the pH value to about 7.5 with ammonia water to free the product:
NH(CH2CH2NH)CH(CH3)CH(CH3) → NH(CH2CH2NH)CH(CH3)CH(CH3) + NH4Cl + HCl
4. Remove insolubles by filtration to obtain free indole-2-carbonyl chloride:
NH(CH2CH2NH)CH(CH3)CH(CH3) → NH(CH2CH2NH)CH(CH3)CH(CH3) + HCl + CO2
5. Dissolve free indole-2-formyl chloride in ethanol and add hydrogen chloride to adjust the pH value to about 5.5 to obtain Tropisetron hydrochloride crystals:
NH(CH2CH2NH)CH(CH3)CH(CH3) + HCl → NH(CH2CH2NH)CH(CH3)CH(CH3)HCl + CO2
Tropisetron Hydrochloride
Tropisetron hydrochloride is a commonly used 5-HT3 receptor antagonist, which is mainly used to prevent and treat nausea and vomiting caused by chemotherapy and radiotherapy. In addition to suppressing the vomiting response, tropisetron hydrochloride has some other reactive properties.
1. Inhibition of 5-HT3 receptors: The main function of tropisetron hydrochloride is to exert an antiemetic effect by inhibiting 5-HT3 receptors. The 5-HT3 receptor is a receptor on the neurotransmitter serotonin that plays a signaling role in the gag reflex. Substances released by tumor cells can activate 5-HT3 receptors, triggering nausea and vomiting. Tropisetron hydrochloride can bind to 5-HT3 receptors, prevent 5-hydroxytryptamine from binding to receptors, and thus inhibit the vomiting response.
2. Act on other receptors: In addition to 5-HT3 receptors, tropisetron hydrochloride can also act on other receptors, such as histamine H1 receptors, dopamine D2 receptors, etc. These effects may cause some adverse reactions, such as headache, drowsiness, dizziness and so on. However, these adverse reactions are generally mild to moderate and require no special treatment.
3. Anti-tumor effect: In recent years, studies have found that tropisetron hydrochloride also has a certain anti-tumor effect. Studies have shown that tropisetron hydrochloride can play an anti-tumor role by inhibiting tumor cell proliferation, inducing tumor cell apoptosis, and inhibiting tumor angiogenesis. These findings provide a new direction for the application of tropisetron hydrochloride.
Immunomodulatory effect: Tropisetron hydrochloride also has a certain immune modulatory effect. Studies have shown that tropisetron hydrochloride can inhibit the proliferation of T lymphocytes and the secretion of cytokines, thereby inhibiting the inflammatory response. This immunomodulatory effect may have potential application value in the treatment of some autoimmune diseases.
5. Effects on the central nervous system: Tropisetron hydrochloride has certain effects on the central nervous system. Studies have shown that tropisetron hydrochloride can inhibit the release of excitatory amino acids in the central nervous system, thereby exerting sedative, hypnotic, and anti-anxiety effects. This effect may in some cases have some impact on the patient's daily life.
Tropisetron Hydrochloride History
Tropisetron hydrochloride is a commonly used 5-HT3 receptor antagonist, which is mainly used to prevent and treat nausea and vomiting caused by chemotherapy and radiotherapy.
1. Discovery and early research: Tropisetron hydrochloride is an indole alkaloid developed by Boehringer Ingelheim, Germany. In the early 1980s, the company began research on 5-HT3 receptor antagonists with the aim of discovering a drug with antiemetic properties. In a large number of compound screening and experiments, they found a compound with higher activity, namely tropisetron hydrochloride.
2. Naming and registration: After the discovery of tropisetron hydrochloride, Boehringer Ingelheim conducted in-depth research and experiments on it. In 1985, the company applied for a patent on tropisetron hydrochloride to the US Food and Drug Administration (FDA), and obtained the patent right in 1987. Subsequently, the company began evaluating the safety and efficacy of tropisetron hydrochloride in clinical trials.
3. Clinical trials: After a series of clinical trials, Tropisetron Hydrochloride was first approved for marketing in Germany in 1994. It was subsequently approved in many other countries as one of the commonly used drugs for the prevention and treatment of nausea and vomiting induced by chemotherapy and radiation therapy.
4. International naming: After Tropisetron Hydrochloride was approved for marketing, the International Nonproprietary Name (INN) named it Tropisetron. INN is an international nonproprietary drug name recognized by the World Health Organization (WHO), which is used to ensure the uniqueness and uniformity of drug names worldwide. The name Tropisetron is named according to its chemical structure characteristics, among which "tropi" comes from "tropic", which means "tropical", indicating that the drug has a chemical structure similar to tropical plants, and "setron" comes from "setäre", which means "tropical". Neurotransmitter", which means that the drug mainly acts on neurotransmitters.
5. Trade name and follow-up research and development: After being named by INN, the trade name of Tropisetron Hydrochloride is widely used. Various pharmaceutical companies market the drug under the name Tropisetron, including Navoban, Torecan, Tropentip, and others. In addition, subsequent research and development has further expanded the scope of application of tropisetron hydrochloride, such as the prevention of postoperative nausea and vomiting.