8-[4-[4-(2-PYRIMIDINYL)-1-PIPERAZINYL]BUTYL]-8-AZASPIRO[4,5]DECANE-7,9-DIONE HYDROCHLORIDE
Buspirone
CAS: 36505-84-7
Molecular Formula: C21H31N5O2
8-[4-[4-(2-PYRIMIDINYL)-1-PIPERAZINYL]BUTYL]-8-AZASPIRO[4,5]DECANE-7,9-DIONE HYDROCHLORIDE - Names and Identifiers
8-[4-[4-(2-PYRIMIDINYL)-1-PIPERAZINYL]BUTYL]-8-AZASPIRO[4,5]DECANE-7,9-DIONE HYDROCHLORIDE - Physico-chemical Properties
| Molecular Formula | C21H31N5O2 |
| Molar Mass | 385.50314 |
| Density | 1.1527 (rough estimate) |
| Melting Point | 105-107 °C(Solv: ethyl acetate (141-78-6)) |
| Boling Point | 511.93°C (rough estimate) |
| Refractive Index | 1.7600 (estimate) |
| Physical and Chemical Properties | Chemical properties white crystal, melting point 104~106 ℃. Buspirone hydrochloride (Buspirone Hydrochloride):C2lH31N5O2?HCI. [33386-08-2]. Crystallized from anhydrous ethanol, melting point 201.5~202.5 ℃. Acute toxicity LD50 rats (mg/kg):136 intraperitoneal injection. |
| Use | Uses a new generation of non-benzodiazepines selective anti-Anxiety agents, which exert an anti-Anxiety effect by affecting the 5-HT (serotonin) system, are partial agonists of the 5-HTIA receptor. Its anti-pyrogenic effect is equivalent to that of diazepam, but without the side effects of diazepam drugs such as anticonvulsant, muscle relaxation, and decreased psychomotor function. It is thus referred to as a selective anti-Anxiety drug. Long use does not produce self-dependence and euphoric effect, the tendency of addiction is small, not easy to cause abuse. For the treatment of acute and chronic Anxiety state, such as Anxiety excitement, inner anxiety and Nervousness state, etc., can also alleviate the Anxiety symptoms with or without depression. |
8-[4-[4-(2-PYRIMIDINYL)-1-PIPERAZINYL]BUTYL]-8-AZASPIRO[4,5]DECANE-7,9-DIONE HYDROCHLORIDE - Risk and Safety
| Hazard Symbols | T - Toxic |
| Risk Codes | 25 - Toxic if swallowed |
| Safety Description | 45 - In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.) |
| UN IDs | UN 2811 6.1/PG 3 |
8-[4-[4-(2-PYRIMIDINYL)-1-PIPERAZINYL]BUTYL]-8-AZASPIRO[4,5]DECANE-7,9-DIONE HYDROCHLORIDE - Upstream Downstream Industry
8-[4-[4-(2-PYRIMIDINYL)-1-PIPERAZINYL]BUTYL]-8-AZASPIRO[4,5]DECANE-7,9-DIONE HYDROCHLORIDE - Security information
| WGK Germany | 3 |
| RTECS number | CL9915000 |
Last Update：2024-04-10 22:29:15
8-[4-[4-(2-PYRIMIDINYL)-1-PIPERAZINYL]BUTYL]-8-AZASPIRO[4,5]DECANE-7,9-DIONE HYDROCHLORIDE - Nature
| storage conditions | Sealed in dry,2-8°C |
| acidity coefficient (pKa) | pKa 7.60±0.01(H2O t=25.0 I =0.1(NaCl)) (Uncertain) |
| NIST chemical information | 8-Azaspiro[4.5]decane-7,9-dione, 8-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-(36505-84-7) |
| EPA chemical information | 8-Azaspiro[4.5]decane-7,9-dione, 8-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]- (36505-84-7) |
Last Update：2024-04-09 20:52:54
8-[4-[4-(2-PYRIMIDINYL)-1-PIPERAZINYL]BUTYL]-8-AZASPIRO[4,5]DECANE-7,9-DIONE HYDROCHLORIDE - Uses and synthesis methods
anxiolytics
Buspirone, also known as butanpirone, Busperone, Buspa, and Cispirone, is a new generation of non-BZ anti-anxiety drugs with anti-anxiety effects, but its mechanism of action is different from benzodiazepine. It mainly acts on 5HT1A receptors and dopamine receptors in the hippocampus, so that the function of serotonin is downregulated to produce anti-anxiety effects. It is a, it has affinity for dopamine receptors and can block dopamine receptors in the presynaptic membrane. At the same time, because this product can reduce the sensitivity of serotonin receptors in the body, it has an antidepressant effect, and can inhibit & gamma;-Aminobutyric acid and make the rigidity flip, it can still affect other neurotransmission systems that act on the midbrain. This product has anti-anxiety effect, does not have hypnotic, muscle relaxation and anticonvulsant effect. It is not suitable for acute cases due to slow onset. It can also be used for anxiety with mild depression. The biggest advantage is that there is no dependence, so there is no risk of abuse.
At therapeutic doses, buspirone has less sedative effect than benzodiazepines. In addition, there is no evidence of physical or psychological dependence or reports of withdrawal syndrome, and its potential abuse is very small even if it is taken by people with large drug dependence. It does not belong to the controlled drug category.
Buspirone has been approved by the US Food and Drug Administration to control anxiety disorders or reduce anxiety symptoms in the short term. Unlike benzodiazepines that have direct anti-anxiety effects, the anti-anxiety effects of buspirone may take 1 to 2 weeks to fully exert, and the somatization symptoms improve more slowly.
Buspirone is only used to treat anxiety disorders in patients over 18 years old and to reduce anxiety symptoms in the short term. The safety and efficacy of the drug in children and adolescents are still unclear.
Pharmacokinetics
oral absorption is fast and complete, reaching the peak blood drug concentration in 0.5~1 hours. There is a liver first pass effect, t1/2 is 1~14 hours, and the plasma protein binding rate is 95%. Most of them are metabolized in the liver, and their metabolites are 5-hydroxybuspirone and 1-(2-pyrimidinyl)-piperazine, which still have certain biological activity. After oral administration, about 60% is excreted by the kidneys and 40% by feces. In liver cirrhosis, due to the decrease of the first pass effect, the blood drug concentration increases, the drug clearance rate is significantly reduced, and the clearance rate is slightly reduced in renal dysfunction. There are no special changes in the kinetics of traditional Chinese medicine in elderly patients.
Azappirone anti-anxiety drugs
Azapyrone anti-anxiety drugs are a new generation of anti-anxiety drugs introduced in recent years. Because of their action on 5-HT1A receptors, also known as 5-HT new anti-anxiety drugs, buspirone and tandospirone As a representative, it is one of the commonly used drugs for the treatment of neurotic disorders. These drugs have anxiolytic effects without sedative/hypnotic and anticonvulsant effects. Buspirone is not as effective as benzodiazepine BDZ for generalized anxiety disorder (GAD), but it is effective for mild GAD, and may be effective for patients with 60% ~ 80% of previous BDZ ineffective. Severe anxiety associated with panic attacks is not as good as BDZ and certain antidepressants. Buspirone alone is not effective in the treatment of obsessive-compulsive disorder, but it has been reported that it has an anti-compulsive effect in combination with 5-HTergic antidepressants. It is also believed that BDZ combined with buspirone may be more effective than either drug alone due to different mechanisms of action. But generally do not advocate joint use.
adverse reactions
common nausea, diarrhea (3%), headache (7%), vertigo (9%), nervousness (4%), agitation (2%) and insomnia. Rare adverse reactions include blurred vision, distraction, malaise (dosage greater than 20 mg), dry mouth, muscle pain, muscle spasm, myotonia, tinnitus, stomach discomfort, sleep disorders, nightmares, dreaminess, fatigue and weakness. Rare adverse reactions include chest pain, confusion, depression, tachycardia, muscle weakness, muscle numbness, and weakness of hands and feet.
precautions
(1) People who are allergic to this product, people with severe liver and kidney insufficiency, patients with acute angle-closure glaucoma, patients with myasthenia gravis, pregnant women, children and adolescents under 18 years old are contraindicated.
(2) Do not drive or operate the machine during medication.
(3) rarely produces dependence.
(4) buspirone has no experience with the following drugs, so be careful when using it: such as antihypertensive drugs, antidiabetic drugs, anticoagulants, contraceptives, cardiac glycosides, etc.
production method
2-aminopyrimidine, concentrated hydrochloric acid and dichloromethane are mixed, zinc chloride is added under stirring, cooled to 5~10 ℃, sodium nitrite is added in batches, and the reaction is continued after addition. Pour into the ice water, let it stand, and separate the organic phase. The aqueous phase is extracted with dichloromethane for 3 times, combined with the organic phase, dried, and evaporated to remove most of the solvent to precipitate light yellow crystals, with a melting point of 63~65 ℃:, which is 2-chloropyrimidine.
Mix anhydrous piperazine, sodium carbonate and water, add 2-chloropyrimidine in batches at 50~65 ℃ and under stirring, continue the reaction after addition, and slowly cool to 35 ℃. 1, 4-bis (2-pyrimidinyl) piperazine was removed by filtration, and the filtrate was extracted 3 times with chloroform. The extract is dried, the solvent is distilled, and the fraction of 115~117 ℃/133Pa (or 118~120 ℃/270Pa) is collected, which is 1-(2-pyrimidinyl) piperazine.
Cyclopentanone, methyl cyanoacetate, cyanoacetamide and formamide are mixed, and triethylamine is slowly added under room temperature stirring to react. Raise the temperature to 60~65 ℃, slowly add water, then add 98% sulfuric acid until the Ph value is 1, cool to 5~10 ℃, filter and wash with water. The obtained solid and sulfuric acid are heated together at 130 ℃, added with water, refluxed at 150 ℃, cooled, filtered, washed with water, recrystallized with crude water and isopropanol to obtain white needle crystal with melting point of 179 ~ 18l ℃ and β,β-tetramethylene glutaric acid. Glutaric acid derivatives and acetic anhydride are heated and refluxed, filtered, concentrated to dry, placed overnight in the refrigerator, precipitated white flake crystals, filtered, dried, and obtained glutaric anhydride derivatives with a melting point of 64~66 ℃. Glutaric anhydride derivatives and concentrated ammonia water are heated to dissolve, quickly poured into a porcelain plate, cooled, and the precipitated scaly crystals are glutarimide derivatives with a melting point of 153~154 ℃. The imine, 1,4-dibromobutane and anhydrous potassium carbonate are refluxed in toluene, filtered, and fractions of 160~1.70 ℃/13Pa are collected as bromobutylated imine compounds. Finally, it is refluxed with 1-(2-pyrimidinyl) piperazine, anhydrous potassium carbonate, and n-butanol, filtered, and evaporated to remove the solvent, and the obtained yellow solid is recrystallized with isopropanol to obtain buspirone, and then It forms a salt with an equimolar ethanol solution of 5mol/L hydrogen chloride, and recrystallizes with anhydrous ethanol to obtain bus.
The 1-(2-pyrimidinyl) piperazine obtained above can be refluxed with 1, 4-dibromobutane, sodium carbonate, and acetonitrile and filtered. Cold to 0 ℃, filter, dry to obtain light yellow crystals, 1-(4-bromobutyl)-4-(2-pyrimidinyl) piperazine, melting point 241.5~242.5 ℃ (or 238~242 ℃). The disubstituted piperazine and the β,β-tetramethylene glutarimide obtained in the previous preparation, anhydrous potassium carbonate, and toluene are refluxed together. Steam to remove toluene, cool, filter the solid, and recrystallize with isopropyl alcohol to obtain white crystal buspirone. Then it reacts with an equimolar ethanol solution of 5mol/L hydrogen chloride to form a salt, and recrystallizes with absolute ethanol to obtain buspirone hydrochloride. The difference between this method and the previous method is that the butyl first introduces the piperazine ring, which seems to be no big difference at first, but it is believed that this method can increase the total yield of the corresponding steps of the previous method from 43.2% to 72.9%. The increase is not small, and the amount of each intermediate is reduced, and the cost is reduced.
Last Update：2024-04-09 21:01:54
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View History
8-[4-[4-(2-PYRIMIDINYL)-1-PIPERAZINYL]BUTYL]-8-AZASPIRO[4,5]DECANE-7,9-DIONE HYDROCHLORIDE
17ALPHA-METHYLTESTOSTERONE
2-甲基丙酸胺
Di(2-propenyl)propanedioic acid dimethyl ester
(6-甲基吡啶-3-基)甲胺
3-(CYCLOPENTYLOXY)-4-METHOXYBENZOIC ACID
258833-04-4
Naphth[2,1-d]isothiazole (8CI,9CI)
十二烷基引发剂
2-ETHYLBUTYRYL CHLORIDE
17ALPHA-METHYLTESTOSTERONE
2-甲基丙酸胺
Di(2-propenyl)propanedioic acid dimethyl ester
(6-甲基吡啶-3-基)甲胺
3-(CYCLOPENTYLOXY)-4-METHOXYBENZOIC ACID
258833-04-4
Naphth[2,1-d]isothiazole (8CI,9CI)
十二烷基引发剂
2-ETHYLBUTYRYL CHLORIDE
Raw Materials for 8-[4-[4-(2-PYRIMIDINYL)-1-PIPERAZINYL]BUTYL]-8-AZASPIRO[4,5]DECANE-7,9-DIONE HYDROCHLORIDE
Dichloromethane
Chloroform
Sodium nitrite
Isopropyl alcohol
Piperazine
2-Aminopyrimidine
2-(1-Piperazinyl)pyrimidine
Glutarimide
Chloroform
Sodium nitrite
Isopropyl alcohol
Piperazine
2-Aminopyrimidine
2-(1-Piperazinyl)pyrimidine
Glutarimide