42971-09-5 Usage
Uses
Used in Pharmaceutical Industry:
Vinpocetine is used as a calcium/calmodulin-dependent phosphodiesterase 1 (PDE1) inhibitor for its neuroprotective and anticonvulsant properties. It helps in reducing inflammation and improving cerebral blood flow, making it a valuable compound in the development of medications for various neurological disorders.
Used in Cerebrovascular Drug Development:
Vinpocetine is used as a cerebrovascular drug, specifically as a vasodilator for the brain. It selectively inhibits vascular smooth muscle calcium dependency phosphodiesterase, increasing the content of cGMP, and expanding cerebral vessels. This, in turn, increases cerebral blood flow and improves cerebral circulation. It is particularly effective for treating dizziness, headache, memory disorders, movement disorders, aphasia, hypertensive encephalopathy, and other conditions related to brain blood circulation障碍 (obstacles).
Used in Neurological Treatments:
As a calcium regulator and a Gleevec metabolite, Vinpocetine is used in the treatment of various neurological conditions. Its ability to regulate calcium levels and act as a tyrosine kinase inhibitor makes it a potential therapeutic agent for diseases involving abnormal cellular signaling and calcium dysregulation.
Used in Research and Development:
Vinpocetine's unique chemical properties and biological activities make it a valuable compound for research and development in the fields of neuroscience, pharmacology, and drug discovery. Its neuroprotective, anticonvulsant, and anti-inflammatory properties are of particular interest for the development of new therapies for neurological disorders and injuries.
Cerebral Vasodilator
Vinpocetine is a cerebrovascular expansion drug and has a relatively stronger function than Vincamine. It can selectively increase cerebral blood flow, enhance and improve brain oxygen supply, promote metabolism, enhance the capacity of deformation for red blood cells, reduce blood viscosity, inhibit platelet aggregation, improve tissue metabolism. Vinpocetine is mainly used in the treatment of cerebral infarction sequela, cerebral hemorrhage sequelae, cerebral arteriosclerosis, etc. It can also used in the treatment of retinal vascular sclerosis and blood vessel spasm, the elderly deafness, and dizziness.
Vinpocetine is a half synthetic Vincamine derivative, and has the similar effect with Vincamine. It has a stronger expansion function for cerebrovascular selectively. Pharmacological effects are as follows:
①Inhibit the activity of calcium dependency phosphodiesterase, increase the content of cAMP which can relax vascular smooth muscle, then relax vascular smooth muscle, and further increase cerebral blood flow.
②Enhance the capacity of deformation of red blood cells, reduce blood viscosity, inhibit platelet aggregation, and thus improve blood flow and microcirculation.
③Promote the brain tissue to absorb glucose, and promote the transformation of brain monoamine metabolism.
④Inhibit the increase of brain lactic acid during cerebral ischemia, increase the ATP content, inhibit the generation of lipid peroxide in the brain, delay the occurring of spasm caused by cerebral ischemia, have the function of improving cerebral metabolism and protecting brain.
Figure 1 is the structural formula of vinpocetine.
Pharmacokinetics
Vinpocetine is of high fat-solubility, easy to be absorbed by the organization, and widely distributed. It can through the blood brain barrier, mainly metabolism to Vinpocetine in the liver, and be excreted by the kidney.
Medicinal properties and Application
Vinpocetine is also called Ethyl apovincaminate, Conway, Karan and Vinpocetine. It is a kind of natural medicine extracted from small vinca flower, and belongs to the indole alkaloids. Can be synthetic now. The mechanism of its pharmacological action is to inhibit the activity of calcium dependency phosphodiesterase, increase the content of CGMP which can relax vascular smooth muscle, then relax vascular smooth muscle, and further increase cerebral blood flow; Enhance the capacity of deformation of red blood cells, reduce blood viscosity, inhibit platelet aggregation, and thus improve blood flow and microcirculation; Promote the brain tissue to absorb glucose, and promote the transformation of brain monoamine metabolism; Inhibit the increase of brain lactic acid during cerebral ischemia, increase the ATP content, increase thedegree of oxygen dissociation in hemoglobin; Increase the resistance capacity for cerebral anoxia and occurring of spasm caused by cerebral ischemia, inhibit the generation of lipid peroxide in the brain. Oral absorption effectively, reach peak at 1 h, then metabolize into Vinpocetine in the body. The half-life of plasma elimination is about 1 hour. For 4 weeks in a row, no accumulation in the body. Clinical used in cerebral infarction sequela, cerebral hemorrhage sequelae, cerebral arteriosclerosis, cerebral vasospasm, brain endarteritis caused vertigo, tinnitus, headache, dizziness, limb numbness, incontinence and other clinical manifestations, depression, anxiety, sleep disorder and other mental symptoms. Clinical experience has shown that it is effective regardless of the length of the course of the disease, and the symptom is fixed or not.
Indications
1.Neurology: all kinds of cerebrovascular disease and its sequelae.
2.Cardiology: coronary heart disease, hardening of the arteries and blood clotting abnormalities, etc.
3.Eye: all kinds of views of visual impairment caused by poor circulation, etc.
4.Otolaryngology: hearing loss, tinnitus, vestibular dysfunction, etc.
5.Neurosurgery: all kinds of craniocerebral surgery back function rehabilitation.
Side Effects
Nervous system: head heavy, dizziness, occasional tiredness and side limb numbness, etc.
Digestive system: nausea, vomiting, loss of appetite, abdominal pain, diarrhea, etc.
Circulatory system: facial blushing, dizziness and other symptoms.
Blood system: white blood cells reduction.
Liver reaction: AST, ALT elevations, rare elevation of alkaline phosphatase.
Kidney reaction: blood urea nitrogen increasing.
Sometimes allergic reactions like skin rash, urticarial and pruritus may appear, then drug should be discontinued. Occasional mild lowering blood pressure, tachycardia, etc.
Production Method
Vincamine extracted from small periwinkle (Vinca mino) of apocynaceae plant as raw material, dehydration to Apovincamine, then hydrolysis to Apovincaminic acid. Dissolved the acid (1.0 g, 0.003 mo1) and 1.0 g of potassium hydroxide in 80 ml of drying ethanol, add bromine ethane (0.4 g, 0.0036 mol), reflux 3 h. After the completion of reaction, cooling, evaporation to dry. Dissolve the leftovers in 500 ml of 2% sulfuric acid, and adjust the Ph to 8. Extracted with methylene chloride, drying with potassium carbonate, after the majority of methylene chloride has been evaporated, add in ethanol. Be placed overnight At 0 oC, filter the collected precipitation crystallization, washing with cold ethanol, drying, 0.66 g of Vinpocetine could be obtained.
Tabersonine extracted from apocynaceae plant willow small licorice leaf or periwinkle seed can also be as raw material, through multi-step synthesis.
Pharmacological Study
Vinpocetine is a synthetic ethyl ester of apovincamine.
Vinpocetine has been used for cognitive impairment, but
the mechanism of action is unclear. A Cochrane review
(Szatmari and Whitehouse, 2003) of three short-term studies
involving 583 patients with dementia (AD, VaD, mixed)
concluded that patients treated with vinpocetine (30–60 mg/
day) showed modest bene t compared to placebo.
Biological Activity
Phosphodiesterase inhibitor, selective for PDE1 (IC 50 = 21 μ M). Also blocks voltage-gated Na + channels.
Biochem/physiol Actions
Ca2+-calmodulin-dependent phosphodiesterase I (PDE1) inhibitor.
References
1) Hagiwara?et al. (1984),?Effects of vinpocetine on cyclic nucleotide metabolism in vascular smooth muscle; Biochem. Pharmacol.,?33?453
2) Molnar and Erdo (1995),?Vinpocetine is as potent as phenytoin to block voltage-gated Na+ channels in rat cortical neurons; Eur. J. Pharmacol.,?273?303
3) Gomez?et al. (2014),?The anti-seizure drugs vinpocetine and carbamazepine, but not valproic acid, reduced inflammatory IL1β and TNF-α expression in rat hippocampus; J. Neurochem.,?130?770
4) Wang?et al. (2014),?Anti-inflammatory effects of vinpocetine on the functional expression of nuclear factor-kappa B and tumor necrosis factor-alpha in a rat model of cerebral ischemia-reperfusion injury; Neuro. Sci. Lett.,?566?247
5) Zhao?et al.?(2011), TSPO-specific ligand vinpocetine exerts a neuroprotective effect by suppressing microglial inflammation; Glia Biol.,?7?187
Check Digit Verification of cas no
The CAS Registry Mumber 42971-09-5 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 4,2,9,7 and 1 respectively; the second part has 2 digits, 0 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 42971-09:
(7*4)+(6*2)+(5*9)+(4*7)+(3*1)+(2*0)+(1*9)=125
125 % 10 = 5
So 42971-09-5 is a valid CAS Registry Number.
InChI:InChI=1/C22H26N2O2/c1-3-22-11-7-12-23-13-10-16-15-8-5-6-9-17(15)24(19(16)20(22)23)18(14-22)21(25)26-4-2/h5-6,8-9,14,20H,3-4,7,10-13H2,1-2H3/p+1/t20-,22+/m1/s1
42971-09-5Relevant articles and documents
Preparation method of vinpocetine
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Paragraph 0051; 0055-0058; 0061-0064; 0067-0070; 0073-0086, (2021/04/10)
The invention provides a preparation method of vinpocetine, which relates to the technical field of synthesis of medical intermediates, and comprises the following steps: (1) respectively feeding an ethanol solution of vincamine and an ethanol solution of sodium ethoxide into a premixer for premixing to form a mixed solution 1; (2) sending the mixed solution 1 obtained in the step (1) to a micro-channel module for complete reaction, and outputting the generated reaction solution to a transfer storage tank; (3) respectively feeding the solution and the mixed acid in the transfer storage tank obtained in the step (2) into a premixer for premixing to form a mixed solution 2; (4) sending the mixed solution 2 obtained in the step (3) to a micro-channel module for complete reaction, and outputting the generated reaction solution to a neutralization kettle; and (5) after the reaction is finished, carrying out post-treatment on the material in the neutralization kettle obtained in the step (4) to obtain the target product vinpocetine. The method has the advantages of high atom utilization rate, high selectivity, high yield and less solid waste, is beneficial to environmental protection, and is convenient for industrial production and utilization.
Method for preparing vinpocetine
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Paragraph 0018; 0141; 0147-0153, (2017/08/29)
The invention relates to a method for preparing a compound, specifically to a method for preparing vinpocetine. The method comprises the following steps: 1) preparation of a vinpocetine crude product, including, mixing an apovincamine ethanol solution and a sodium ethoxide ethanol solution for a reflux reaction, removing the solvent, adding ethanol, carrying out a reflux reaction of the sodium ethoxide ethanol solution, when the residual content of apovincamine is less than 0.3% of the added apovincamine raw material, performing hot filtration, removing a part of solvent of the filtered liquid, and performing cooling crystallization, solid-liquid separation, washing and drying to obtain the vinpocetine crude product; and 2) refining of vinpocetine, including adding active carbon, performing hot filtration, and performing recrystallization with ethanol for refining to obtain vinpocetine. The method is short and simple in process. The prepared vinpocetine is high in yield and purity, meets the standard of the European Pharmacopoeia (EP) 6.0, and is easy for industrial production.
A semi-synthetic synthesis process of vinpocetine
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Paragraph 0012; 0013, (2017/03/14)
The invention provides a vinpocetine semisynthesis process. The vinpocetine is obtained through hydrolysis, dehydration and esterification reactions by a one-pot method, and after the reactions are finished, extraction separation, purification and crystallization are performed, and finally, the high-content and high-purity product can be obtained. The method is few in reaction steps, simple in process flow, high in vinpocetine yield, simple in equipment, and green and environment-friendly in production procedure, and has tremendous economic and social benefits.
Process for the preparation of vinpocetine and apovincamine
-
Page/Page column 7, (2010/04/25)
A process for the preparation of vinpocetine and apovincamine, wherein said process comprises the steps of: (1) preparing a solution of the compound of formula (II) below and an organic or inorganic base in a polar aprotic solvent, and (2) adding an alkyl haloacetate to the solution of step (1) under controlled temperature conditions.
Compositions of a cyclooxygenase-2 selective inhibitor and a sodium ion channel blocker for the treatment of pain, inflammation or inflammation mediated disorders
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, (2008/06/13)
The present invention provides compositions and methods for the treatment of pain, inflammation or inflammation-mediated disorders in a subject. More particularly, the invention provides a combination therapy for the treatment of pain, inflammation or inflammation mediated disorders comprising the administration to a subject of a sodium ion channel blocker in combination with a cyclooxygenase-2 selective inhibitor.
APOVINCAMINIC ACID DERIVATIVE AND MEDICINE CONTAINING THE SAME
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, (2008/06/13)
This invention relates to an apovincaminic acid derivative represented by the following formula (1): wherein R1represents a lower alkyl group, and R2represents an aryl group, which may be substituted by 1 to 5 substituents selected from halogen atoms and lower alkyl, lower alkoxy, lower alkoxycarbonyl, acylamino and nitro groups, a benzyl group, a quinolyl group or a thienyl group, or an acid addition salt thereof; and also to a drug containing the same. This compound has excellent vasodilating activity and platelet aggregation inhibiting activity, and can be used for the treatment of cerebrovascular disorder, thromboembolism and chronic arterial occlusive diseases and also for the improvement of blood flow disturbances.
A facile one-pot synthesis of vinpocetine
Kuge,Nakazawa,Kometani,Sugaya,Mochida,Tomioka
, p. 759 - 766 (2007/10/02)
A one-pot synthesis of vinpocetine from vincamine was established. Lewis acids caused transesterification and/or dehydration of vincamine in EtOH. FeCl3 catalyzed both transesterification and dehydration while Ti(OEt)4 selectively catalyzed transesterification.
Syntheses and Cardiovascular Activity of Stereoisomers and Derivatives of Eburnane Alkaloids
Czibula, Laszlo,Nemes, Andras,Visky, Gyoergy,Farkas, Maria,Szombathelyi, Zsolt,et al.
, p. 221 - 230 (2007/10/02)
The synthesis of all the possible isomers of the eburnamenine-vincamine type alkaloids 1b, 2a*, 3a and derivatives 4, 8, 9, 10 is described.Structures were determined by 1H- and 13C-NMR spectroscopy including special techniques such as DR, DEPT, DNOE, and 2D-HSC.In contrast to the known cerebrovascular effects of cis-(3S,16S) compounds, trans-(3S,16R) derivatives show a significant peripheral vasodilator effect. Key Word: Eburnanes / Alkaloids / Cardiovascular effects / Indoloquinolizines
Synthesis of vinca alkaloids and related compounds, XV. A new synthetic route to (+)-vincaminic and (+)-apovincaminic esters
Szabo,Kalaus,Szantay
, p. 629 - 638 (2007/10/02)
Esters of types 7 and 8, possessing excellent vasodilating effects, have been prepared. A method has been found for the resolution of methyl ester 7c. A new method is described for the preparation of the lactam (+)-10 and its conversion to the oxime (+)-11, from which (+)-vincamine (1a) and the (+)-apovincaminic esters 2a,b were synthesized.
