82571-53-7 Usage
Platelet aggregation inhibitor
Ozagrel and clopidogrel, cilostazol, aspirin enteric-coated tablets are commonly used in China at present as platelet aggregation inhibitor, Ozagrel is an anti-thrombosis drug which belongs to a thromboxane alkyl cyclooxygenase (TXA2) inhibitors, originally it was successfully developed by Japan Ono pharmaceutical Co., Ltd. and Kissei pharmaceutical Co., Ltd. ,it was approved for marketing in Japan in 1988. At present, domestic manufacturers include the Liaoning dandong, medical and pharmaceutical industry, Shandong Elohim Pharmaceutical Co., Changchun fine distinctions Pharmaceutical, Dalian Metro big pharmaceutical companies, pharmaceutical Shenyang Jishi, Hainan bikai Pharmaceutical, Changchun Haobang Pharmaceutical and Shandong HuaLu pharmaceutical. Modern medicine has proved that platelets play an important role in the process of atherosclerosis and thrombosis, the effective regulation of platelet can play a multiplier effect on blood vessel lumen stenosis, emboli and diseases caused by occlusion of blood circulatory system . At present, the platelet aggregation inhibitor drugs used clinically are mainly cyclooxygenase (TXA2) inhibitors, phosphodiesterase (PDE) inhibitors, adenosine diphosphate (ADP) receptor antagonists, platelet fibrinogen antagonists drugs.
Ozagrel sodium salt has a strong antithrombotic effect, which is the world's first listing inhibitor of the potent thromboxane synthase feature ,it has the inhibiting effect on the platelet aggregation induced by different inducers (such as collagen, arachidonic acid, epinephrine, ADP, 5-HT, etc.) ,it can inhibit TXA2 synthase, while it can promot the generation of PGI2, it has effect on anti-platelet aggregation and relieving the vasospasm, it can inhibit the cerebral thrombosis and cerebral vasospasm. It is Mainly applied to the improvement of subarachnoid hemorrhage after cerebral vasospasm and cerebral ischemic symptoms. It can reduce cerebral infarction fibrin, and factor I,it can reduce blood viscosity and inhibit platelet aggregation.in the cerebral embolism model tests caused by the injection of arachidonic acid , after taking the product ,the occurrence of cerebral thrombosis is suppressed , animal mortality is decreased, while not only the cerebral movement disorders of acute phase is improved , but also the circulatory disorders of the acute phase of cerebral ischemia are improved,and the energy metabolism of cerebral ischemia is improved. Common agents are ozagrel injection, each 20mg.it is diluted by physiological saline or glucose injection then intravenous infusion, every day 80mg. when it is combined with other anti-platelet drugs, the dose of this product should be reduced. There may be bleeding tendency; occasional allergy, liver dysfunction, blood pressure drops, the outdoor contraction, headache, injection site pain, abdominal distension and other adverse reactions. Hemorrhage patients (intracerebral hemorrhage, intraventricular hemorrhage, gastrointestinal bleeding, subcutaneous bleeding, etc.), pregnant women or potentially pregnant women and children should use with caution. And it has a synergistic effect with drugs having inhibition of platelet function ,when they are used together, there must be appropriate reduction. Avoid mixing injection with calcium solution (Green solution, etc.) in order to avoid opacification.
The above information is edited by the lookchem of Tian Ye.
Chemical Properties
Obtain prismatic crystals From ethanol-diethyl ether , melting point 223~224 ℃.
Hydrochloric acid Ozagrel (Ozagrel Hydrochloride): C13H12N2O2 HCl. [78712-43-3]. crystallization From ethanol-ethyl ether , melting point 214~217 ℃.
Ozadrel Sodium: C13 H11N2NaO2. White crystal or crystalline powder, odorless, Pickle bitter. Soluble in water, soluble in methanol, insoluble in ethanol, acetone or ether. Acute toxicity LD50 male and female mice, male and female rats (mg/kg): 1940,1580,1150,1300 intravenous injection; 3800.3600.5900,5700 oral; 2450,2100,2300,2250 subcutaneous injection.
Uses
Different sources of media describe the Uses of 82571-53-7 differently. You can refer to the following data:
1. Strong thromboxane synthetase inhibitors. By inhibiting thromboxane synthase,it reduces the body thromboxane A, (TXA2), and promotes prostacyclin (PGl2) generation to be against aggregation of platelets, and cerebrovascular spasm, and it almost has no effect on cyclooxygenase and other arachidonic metabolizing enzymes.it is Clinically used for improving cerebral vasospasm after cobweb inferior vena hemorrhage surgery and symptoms of cerebral ischemia associated with cerebral vasospasm, and dyskinesia associated with cerebral thrombosis acute phase.
2. Ozagrel is a potent and selective thromboxane A2 inhibitor. Used in the prevention of ischemic stroke injury and maintains a strong effect in vascular contraction and vascular endothelial cell dysfunction.
production method
Use dehydrated methyl benzaldehyde as materials,after condensation with acetic anhydride aldol ,form 3-tolyl acrylate, become into a 3--tolyl acrylate ethyl after esterification , use benzoyl peroxide as an initiator, with N-bromosuccinimide (NBS) ,make the methyl on the ring become into bromomethyl, and after the hydrolysis reaction with imidazole, ozagrel sodium is obtained , melting point 308 ℃ (decomposition).
Description
Ozagrel sodium is the first thromboxane (TX2) synthetase inhibitor to be developed as an
antithrombotic agent. In patients with angina pectoris, ozagrel sodium reportedly
decreases the frequency of anginal attacks and increases exercise tolerance. Other
indications for ozagrel sodium currently under study include bronchial asthma and
pulmonary thromboembolism.
Brand name
Xanbon; Cataclot
Check Digit Verification of cas no
The CAS Registry Mumber 82571-53-7 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 8,2,5,7 and 1 respectively; the second part has 2 digits, 5 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 82571-53:
(7*8)+(6*2)+(5*5)+(4*7)+(3*1)+(2*5)+(1*3)=137
137 % 10 = 7
So 82571-53-7 is a valid CAS Registry Number.
InChI:InChI=1/C13H12N2O2/c16-13(17)6-5-11-1-3-12(4-2-11)9-15-8-7-14-10-15/h1-8,10H,9H2,(H,16,17)/b6-5+
82571-53-7Relevant articles and documents
Synthesis method of ozagrel sodium
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Paragraph 0048-0049, (2020/07/12)
The invention discloses a synthesis method of ozagrel sodium, and belongs to the technical field of medicines. The synthesis method comprises the following steps: (1), taking 4-bromobenzyl bromide asa starting material, and reacting with imidazole under an alkaline condition to generate a 1-(4-bromobenzyl)-1H-imidazole intermediate 1; (2), enabling 1-(4-bromobenzyl)-1H-imidazole to react with acrylate under the catalysis of palladium acetate to generate an ozagrel ester intermediate 2; and (3), carrying out alkaline hydrolysis on ozagrel ester to obtain an ozagrel sodium product. The synthesis method disclosed by the invention has the advantages of easily available raw materials, low price cost, few steps, small pollution and the like, and is suitable for industrial production.
Preparation method of ozagrel
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Paragraph 0046; 0047; 0048; 0049; 0050; 0051; 0052; 0053, (2017/06/29)
The invention provides a preparation method of ozagrel, which is characterized by comprising the following steps of: adding ozagrel hydrochloride monohydrate into purified water, heating to dissolve the ozagrel hydrochloride monohydrate, adding alkali liquor, carrying out cooling and crystallization after stirring, and carrying out extraction filtration to obtain an ozagrel crude product; carrying out recrystallization on the ozagrel crude product in mixed solution of methyl alcohol and water to obtain an ozagrel finished product. The preparation method is simple and efficient to operate and easy to control, and purity of the obtained ozagrel accords with the requirements of the Japanese pharmacopoeia.
Highly selective inhibitors of thromboxane synthetase. 1. Imidazole derivatives
Iizuka,Akahane,Momose,Nakazawa,Tanouchi,Kawamura,Ohyama,Kajiwara,Iguchi,Okada,Taniguchi,Miyamoto,Hayashi
, p. 1139 - 1148 (2007/10/02)
The structure-activity relationships of imidazole derivatives as inhibitors of thromboxane (TX) synthetase were investigated. Introduction of various substituents (e.g., one or two methyl groups, a halogen atom, a methylidene group, unsaturated bonds, or a phenylene group) into the α position or other positions in the carboxy-bearing side chain of 1-(7-carboxyheptyl)imidazole was found to increase the inhibitory potency. The length of the side chains with the phenylene group was optimum for the inhibitory potency on TX synthetase in the region of 8.5-9.0 A. Among the tested imidazole derivatives, 1-(7-carboxy-7-methyl-2-octynyl)imidazole, 4-[3-(1-imidazolyl)-propyl]benzoic acid, and (E)-4-(1-imidazolylmethyl)cinnamic acid and its α-methyl analogue showed the highest potency with an IC50 in the range of 10-8 to 10-9 M. Inhibition by these derivatives was highly selective for the TX synthetase, since other enzymes such as fatty acid cyclo-oxygenase and prostacyclin synthetase were not affected.
