27848-84-6

Basic information

• Product Name: Nicergoline
• Synonyms: (+)-10-methoxy-1,6-dimethylergoline-8-beta-methanol5-bromonicotinate;10-methoxy-1,6-dimethyl-ergolin-8-beta-methanol-(5-bromnicotinat);10-methoxy-1,6-dimethyl-ergoline-8-beta-methano5-bromo-3-pyridinecarboxy;10-methoxy-1,6-dimethyl-ergoline-8-beta-methano5-bromonicotinate(ester);10-methoxy-1,6-dimethylergoline-8-methanol5-bromo-3-pyrindinecarboxylate(es;1-methyl-lumilysergol8-(5-bromonicotinate)10-methylether;8-beta-((5-bromonicotinoyloxy)methyl)-1,6-dimethyl-10-alpha-methoxyergoline;fi6714
• CAS NO: 27848-84-6
• Molecular Formula: C₂₄H₂₆BrN₃O₃
• Molecular Weight: 484.39
• EINECS: 248-694-6
• Product Categories: Miscellaneous Natural Products;Miscellaneous;Adrenoceptor;SPIROPITAN
• Mol File: 27848-84-6.mol
• Article Data: 10

Chemical Properties

• Melting Point: 136-138°
• Boiling Point: 594.4 °C at 760 mmHg
• Flash Point: 313.3 °C
• Appearance: /
• Density: 1.3558 (rough estimate)
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.6200 (estimate)
• Storage Temp.: 2-8°C
• Solubility: Practically insoluble in water, freely soluble in methylene chloride, soluble in ethanol (96 per cent).
• PKA: 6.33±0.40(Predicted)
• Water Solubility: Soluble in alcohol, chloroform, and acetone. Insoluble in water.
• Merck: 14,9496
• CAS DataBase Reference: Nicergoline(CAS DataBase Reference)
• NIST Chemistry Reference: Nicergoline(27848-84-6)
• EPA Substance Registry System: Nicergoline(27848-84-6)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: 36
• RIDADR: 1544
• WGK Germany: 3
• RTECS: KE6341000
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 27848-84-6(Hazardous Substances Data)

Usage

Chemical Properties

Fine to granular, white or yellowish powder.

Originator

Sermion,Farmitalia,Italy,1974

Uses

Different sources of media describe the Uses of 27848-84-6 differently. You can refer to the following data:
1. antipsychotic
2. Nicergoline is a drug used for age-dependent cognitive impairment such as Alzheimers disease and other types of dementia. Nicergoline has shown to protect cultured neurons against β-amyloid toxicity. Nicergoline protects against neuronal cell death induced by activated microglia and astrocytes through the inhibition of inflammatory mediators and the upregulation of neurotrophic factors by glial cells. Nicergoline is a drug used for age-dependent cognitive impairment and it protects cultured neurons against β-amyloid toxicity.

Manufacturing Process

Preparation of 1-Methyl Lumilysergic Acid 8-Methyl Ester-10-Methyl Ether: Into a suspension of 10 grams of 1-methyl-lumilysergic acid in 600 cc of absolute methanol a stream of anhydrous hydrogen chloride is bubbled for 1.5 hours with strong cooling. The stream of hydrogen chloride is stopped and the mixture is allowed to stand for 30 minutes at 0°C, and is evaporated in vacuo to dryness. The residue is taken up with ice-cooled water made alkaline with concentrated ammonia and extracted with chloroform. The combined chloroform extracts are washed first with a 5% aqueous solution of sodium bicarbonate, then with water, and are thereafter dried over anhydrous sodium sulfate and finally evaporated in vacuo to dryness.Preparation of 1-Methyl Lumilysergol-10-Methyl Ether: To a boiling suspension of 2 grams of lithium aluminum hydride in 50 cc of anhydrous tetrahydrofuran, a solution of 1 gram of 1-methyl lumilysergic acid-8-methyl ester-10-methyl ether in 20 cc of anhydrous tetrahydrofuran is added dropwise and the resulting solution is refluxed for a further 2 hours. After cooling the resulting solution, aqueous tetrahydrofuran is added to destroy the excess reducing agent and the solution is filtered. Tetrahydrofuran is distilled off and the residue is recrystallized from acetone petroleum ether.Preparation of Nicergoline: To a solution of 1-methyl lumilysergol-10-methyl ether in pyridine, 5-bromonicotinyl chloride is used as an acylating agent at room temperature. The mixture is stirred for 1 hour. Water and methanol are added and the resulting mixture is stirred for 1 hour, extracted with chloroform, and washed in sequence with 1% aqueous caustic soda, 5% aqueous sodium bicarbonate solution, and water. The resulting solution is dried over anhydrous sodium sulfate and the solvent is distilled off. By recrystallization of the residue from acetone petroleum ether, nicergoline is obtained, melting at 136° to 138°C.

Brand name

Sermion (Farmitalia, Societa Farmaceutici Italia, Italy).

Therapeutic Function

Vasodilator

Biological Activity

α -adrenergic, vasodilator. Cognitive enhancer.

Pharmacology

Nicergoline is an ergot derivative that may protect against degeneration of cholinergic neurones (Giardino et al.,2002). Nicergoline has a broad spectrum of action (Winblad et al,2008): (1) as a1-adrenoceptor antagonist it induces vasodilatation and increases arterial blood flow; (2) it enhances cholinergic and catecholaminergic neurotransmission; (3) it inhibits platelet aggregation; (4) it promotes metabolic activity, resulting in increased oxygen and glucose utilization; and (5) it has neurotrophic and antioxidant properties. Nicergoline has been used for the treatment of various dementias, including AD and VaD (Fioravanti and Flicker, 2001). The therapeutic effects of nicergoline were evident by 2 months of treatment and were maintained for 6-12 months.

Safety Profile

Poison by intravenous route. Moderately toxic by ingestion and subcutaneous routes. An experimental teratogen. Other experimental reproductive effects. A vasodilator. When heated to decomposition it emits very toxic fumes of Brand NOx.

InChI:InChI=1/C24H26BrN3O3/c1-27-13-17-8-21-24(30-3,19-5-4-6-20(27)22(17)19)9-15(12-28(21)2)14-31-23(29)16-7-18(25)11-26-10-16/h4-7,10-11,13,15,21H,8-9,12,14H2,1-3H3/p+1/t15-,21-,24+/m1/s1

Upstream product

• 74-88-4 methyl iodide 
• 53375-83-0 10-methoxy-1,6-dimethyl-ergoline-8-carboxylic acid methyl ester 
• 23495-64-9 10α-methoxy-9,10-dihydrolysergic acid methylester 
• 29681-44-5 5-bromo-3-pyridine carboxylic acid methyl ester 
• 35155-28-3 1-Methyl-10alpha-methoxy-9,10-dihydrolysergol 
• 5572-96-3 1-Methyllysergol 
• 20826-04-4 5-bromo-3-pyridinecarboxylic acid 
• 602-85-7 lysergol 
• 39620-02-5 5-bromonicotinoyl chloride 

Downstream Products

• 20826-04-4 5-bromo-3-pyridinecarboxylic acid 
• 35155-28-3 1-Methyl-10alpha-methoxy-9,10-dihydrolysergol 

Relevant articles and documents

Nicergoline synthesis method

The invention belongs to the technical field of raw material medicine synthesis, and particularly relates to a nicergoline synthesis method, which comprises the following steps: (1) methylating nitrogen-hydrogen bonds in 10-methoxyl-methyl ergoate to obtain a; (2) reducing an ester group in a into a hydroxyl group to obtain b; and (3) acylating the hydroxyl in the b. The nicergoline synthesized by the synthesis method is high in purity, methyl ether impurities can be effectively avoided, reaction conditions are mild and controllable, industrial large-scale production of the nicergoline raw material medicine is facilitated, and the method plays a positive role in promoting improvement of the quality of the nicergoline raw material medicine and reducing side effects and risks of medication of patients.

Improved preparation method of nicergoline (by machine translation)

Compared the prior art,bromonicotinoyl chloride intermediate, is prepared-methoxyphenylglycinol :(1) by a reaction with an organic amine as, an acid-binding agent, to produce 10α -(2) methyl - 101010101010101010and X3B1,methoxyphenylglycinol, in a solvent, 10α - The final yield of the product can reach or above product to be 1 - suitable for large-scale ;(3) production, The, method 5 - comprises the following 5 - steps 5 - carrying out a methylation reaction 1 - with an organic, amine, as an organic amine as an acid,binding compound, in a solvent in a solvent and an inorganic base by an organic amine as an acid-binding agent in, an amide type non-protonic solvent to prepare 50% the . nylmyralyl chloride 99%, midst with an organic amine as an organic amine as an acid-binding agent. (by machine translation)

Synthetic method of nicergoline

The invention discloses a synthetic method of nicergoline. The synthetic method comprises the following steps: (1) photocatalytic addition reaction; (2) purification of 10-methoxy-dihydroergosterol; (3) methylation reaction; (4) purification of 10-methoxy-1, 6-dimethane-8-carbinol-ergoline; (5) esterification reaction; and (6) purifying of the nicergoline. According to the Synthetic method of thenicergoline, the mild photocatalytic addition, methylation and esterification reactions in the reaction process are adopted, and the raw materials and reagents with high safety are selected, so that the whole synthesis process is safe and controllable, the post-processing process is simplified, and the product obtained by the reaction is high in yield, high in purity, good in quality and suitablefor industrial production.