methyl 3-(4-((S)
Landiolol hydrochloride
CAS: 144481-98-1
Molecular Formula: C25H40ClN3O8
methyl 3-(4-((S) - Names and Identifiers
| Name | Landiolol hydrochloride |
| Synonyms | methyl 3-(4-((S) Ono 1101 hydrochloride Landiolol hydrochloride propanoate hydrochloride -2,2-Dimethyl-1,3-dioxolan-4-yl) -2-hydroxy-3-((2-(morpholine-4-carboxamido) [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl 3-[4-[(2S)-2-hydroxy-3-[2-(morpholine-4-carbonylamino)ethylamino]propoxy]phenyl]propanoate hydrochloride Benzenepropanoic acid, 4-(2-hydroxy-3-((2-((4-morpholinylcarbonyl)amino)ethyl)amino)propoxy)-, (2,2-dimethyl-1,3-dioxolan-4-yl)methyl ester, (S-(R*,R*))-, hydrochloride |
| CAS | 144481-98-1 |
| EINECS | 1308068-626-2 |
| InChI | InChI=1/C25H39N3O8.ClH/c1-25(2)35-18-22(36-25)17-34-23(30)8-5-19-3-6-21(7-4-19)33-16-20(29)15-26-9-10-27-24(31)28-11-13-32-14-12-28;/h3-4,6-7,20,22,26,29H,5,8-18H2,1-2H3,(H,27,31);1H/t20-,22+;/m0./s1 |
methyl 3-(4-((S) - Physico-chemical Properties
| Molecular Formula | C25H40ClN3O8 |
| Molar Mass | 546.05 |
| Melting Point | 125.4° |
| Boling Point | 727.5°C at 760 mmHg |
| Flash Point | 393.8°C |
| Solubility | DMSO (Slightly), Ethanol (Slightly, Sonicated) |
| Vapor Presure | 3.24E-22mmHg at 25°C |
| Appearance | Solid |
| Color | White to Off-White |
| Storage Condition | Refrigerator |
methyl 3-(4-((S) - Risk and Safety
| RTECS | DA8346700 |
| Toxicity | LD50 in mice (mg/kg): 290 i.v. (Iguchi) |
methyl 3-(4-((S) - Reference Information
| overview | landiolol hydrochloride (Landiolol hydrochloride), trade name Onoact 50, is an ultra-short-acting and highly selective β1 receptor blocker, mainly antagonizing the β1 receptor present in the heart, and improving tachycardia by inhibiting the increase in cardiac beats caused by catecholamines. Developed by Japan's Ono Pharmaceutical Industry Company, it was first listed in Japan in September 2002. It is mainly used clinically for emergency treatment of tachycardia arrhythmias (including atrial fibrillation, atrial flutter, sinus tachycardia) during surgery. Emergency treatment of tachycardia arrhythmias (including atrial flutter, atrial fibrillation, sinus tachycardia) under dynamic monitoring of the circulation after surgery. |
| preparation method | 1. synthesis of compound 3 adding compound 2(29.4g,0.49 mol) and dichloromethane (500ml) to a 1000ml three-neck bottle equipped with a stirrer and thermometer, cooling to -5 ℃ under stirring, starting to dropwise add dichloromethane (250ml) solution of ditert-butyl dicarbonate (4.27g,0.025 mol), during the dropping process, the temperature is controlled below 15 ℃, and the adding is completed in about 4 h, and then stirred at room temperature for 16 h. The organic layer is washed with water (300ml × 3) and dried with anhydrous sodium sulfate, and the dichloromethane is evaporated under reduced pressure to obtain white oil. 2. Synthesis of Compound 6: Add compound 4(20g,0.12 mol) and dichloromethane (200 ml) into a 500ml three-neck bottle, add methylene chloride (50 ml) solution of compound 5(10.7g,0.12 mol) dropwise under stirring, add it for about 1 h, and then stir for 6 h. Wash the dichloromethane layer with water (100 ml × 1), wash the water layer with dichloromethane (60 ml × 3) after liquid separation, combine the organic layers, dry with anhydrous magnesium sulfate, and evaporate the dichloromethane under reduced pressure to obtain white solid compound 6. 3. Synthesis of Compound 7 Dichloromethane (100 ml) is added to a 250ml three-neck bottle, compound 3(7.85g,0.049 mol) is added to dissolve under stirring, and dichloromethane (50 ml,0.78 mol) solution of compound 6(8.8g,0.049 mol) is added dropwise under stirring, the addition is completed in about 1 h, and the temperature is raised to reflux reaction for 36 h. Wash with dilute hydrochloric acid aqueous solution (100 ml × 3), dry the organic layer with anhydrous magnesium sulfate, evaporate dichloromethane under reduced pressure to obtain oil, which is confirmed as compound 7 by MS. 4. Synthesis of Compound 8 Compound 7(11.3g,0.041 mol) and ethyl acetate (100 ml) are added to a 250ml three-neck bottle, heated to reflux, oxalic acid (7.5g,0.083mol) is added under stirring, catalytic trifluoroacetic acid is added, and reflux reaction is carried out for 2 h. Filtered while hot to get white solid compound 8. 5. Synthesis of Compound 9 Add compound 8(5.7g,0.026 mol) and methanol (50 ml) to a 100ml single-neck bottle equipped with a stirrer, add sodium hydroxide solid (4g,0.1mol) under stirring, and stir at room temperature for 5 h. Filtering, decompressing and volatilization of methanol, then dissolving with dichloromethane, filtering, and the filtrate is spin-dried to obtain light yellow oil, which is confirmed by MS as compound 9. 6. Synthesis of Compound 1 Add compound 9(1.4g,0.008 mol) and isopropanol (5 ml) to a 15ml three-neck bottle equipped with a stirrer, raise the temperature to 50 ℃, add compound 10(1.5g,0.004 mol) dropwise under stirring, and monitor the reaction for 3 h by high performance liquid chromatography. After decompressing and drying isopropanol at 40 ℃, it is redissolved with water (5 ml). The water layer is extracted with ethyl acetate (10 ml × 3) and the ethyl acetate layer is combined. The ethyl acetate layer was washed with saturated ammonium chloride solution (10ml × 3) at room temperature (25 ℃), dried with anhydrous sodium sulfate, and dried at 40 ℃ to obtain white solid (2.02g, yield 80%, melting point: 125 ℃)(yield 68%, melting point 125.4 ℃). The synthesized white solid (2.02g) and ethyl acetate (3 ml) are added to a 10 ml round bottom flask, heated to reflux for 3 min, then cooled to room temperature, and filtered to obtain the final product landiolol hydrochloride. Fig. 1 is a route map for the synthesis of landiolol hydrochloride |
| pharmacological action | 1. effect on heart (1) effect on myocardial ischemia cardioprotective effect in myocardial ischemia and reperfusion. (2) The effect on arrhythmia can prevent atrial fibrillation after coronary artery bypass grafting (CABG). (3) Mitral valve systolic forward motion After valvuloplasty, the mitral valve systolic forward motion occurs, which often leads to the collapse of hemodynamics. Catecholamine combined with landiolol hydrochloride can eliminate the mitral valve systolic forward movement and quickly restore the circulation collapse, indicating that landiolol is effective in preventing the occurrence of mitral valve systolic forward movement. 2. Effects on hemodynamics Changes in hemodynamics will increase myocardial oxygen consumption and bring risks. Landiolol can inhibit the hemodynamic response caused by local penetration of epinephrine, laryngoscopy, tracheal intubation, awakening from anesthesia, and tracheal extubation; continuous perfusion can also inhibit the hemodynamic response of anesthesia during craniotomy, Maintain arterial blood pressure and cerebral oxygen balance during craniotomy; for patients with different heart states, in patients with normal heart function, the rate of tachycardia during surgery can be reduced without aggravating hemodynamics, patients with ejection fraction (EF)<50% before surgery should pay attention to the reduction of blood pressure and the weakening of heart function; while fully controlling the hypertension of elderly patients before surgery, when they wake up from anesthesia, landiolol can make hemodynamics more stable. 3. Effects on the uterus Landiolol should be safe for pregnant women because it has no side effects on the baby. In addition, due to the high selectivity of landiolol to β1-receptor, the effect on uterine contraction is very weak. Landiolol can also be used safely during cesarean section in patients with hypertrophic infarct cardiomyopathy, while effectively controlling paroxysmal tachycardia. 4. Effects on the brain. Administration before ischemia has a neuroprotective effect on transient cerebral ischemia in rats. 5. Other effects Landiolol helps the treatment of patients with sepsis by inhibiting the inflammatory response, while improving lung injury and cardiac function. Continuous perfusion of landiolol can reduce the amount of anesthetic used in patients under general anesthesia. Due to its high selectivity to β1-receptor, landiolol can replace prunelol and be used safely in patients with airway hyperresponsiveness before surgery and in intensive care units. |
| pharmacodynamic | metabolism: this product is rapidly metabolized after hydrolysis in human liver and plasma. The clearance rate of liver metabolism is the hepatic blood flow rate, which accounts for about half of the total clearance rate. In vitro plasma, t1/2 metabolized by this product is 4.1 minutes. It is inferred that the main metabolic enzymes of this product in human liver and plasma are carboxylesterase and cholinesterase respectively. Excretion: The main excretion route of this product is urine. If the intravenous infusion of 0.04 mg/kg per minute is used for 60 minutes, healthy adults will excrete about 99% from urine after 24/hour and 24 hours of medication. The prototype drug in urine accounts for 8.7%, and the main metabolite is carboxylate. |
| apply | for emergency treatment of tachycardia arrhythmia (including atrial fibrillation, atrial flutter, sinus tachycardia) during surgery. Emergency treatment of tachycardia arrhythmia (including atrial flutter, atrial fibrillation, sinus tachycardia) under dynamic monitoring of circulation after surgery. (2015-12-21) |
| Precautions | 1. This product is contraindicated in patients with the following diseases: cardiogenic shock; metabolic acidosis such as diabetic ketosis; Atrioventricular block above grade II bradycardia arrhythmias such as sinus dysfunction syndrome; right heart dysfunction caused by pulmonary hypertension; congestive cardiac insufficiency. In addition, untreated patients with pheochromocytoma and those with a history of allergy to this product are prohibited. 2. The following patients: patients with left ventricular systolic dysfunction; patients with bronchospasm; patients with diabetes who have not been well controlled; patients with hypotension; patients with severe blood, liver, and kidney insufficiency; peripheral circulation disorders such as gangrene, Raynaud's syndrome, Intermittent claudication, etc.; patients; patients with heavy bleeding or symptoms of dehydration, etc. should be used with caution. 3. Basic precautions:(1) According to cardiac and electrogram monitoring, blood pressure measurement and cardiac function testing medication. When blood pressure is reduced or bradycardia, the dose should be reduced or discontinued, and corresponding measures should be taken when necessary. (2) Patients with angina pectoris will worsen their condition when they rapidly stop using drugs such as prozylol hydrochloride, and there are reports of myocardial infarction. Therefore, careful observation must be made when stopping this product. (3) For patients with atrial fibrillation and atrial flutter, attention should be paid to the reduction of cardiac beats. (4) This product is only suitable for short-term emergency treatment. The use time is generally 5-10 minutes, and the patient's state needs to be closely observed. This product cannot be used after the emergency period. (5) The effect of this product on reducing the number of heart beats is rapidly weakened after stopping the drug, until it disappears after 30-60 minutes. Attention should be paid to observation. |
| drug interaction | 1. the combination of reserpine, a drug that inhibits sympathetic nervous system, and this product may cause excessive sympathetic nerve inhibition, which needs to be reduced with caution. 2. hypoglycemic drugs such as insulin. When combined with this product, it may cause tachycardia due to hypoglycemia. Attention should be paid to monitoring blood sugar during treatment. 3. It has synergistic effect with calcium antagonist verapamil and diltiazem. Severe hypotension, bradycardia, and cardiac insufficiency may occur in patients with congestive cardiac insufficiency, sinus block, and atrioventricular block, and should be reduced with caution. 4. Combined with digoxin can prolong the atrioventricular conduction time, which needs to be reduced with caution. 5. Combined with L-type antiarrhythmic drugs such as propithamide, procainamide and jamaline may cause excessive inhibition of cardiac function, which should be reduced with caution. 6. Combined with clonidine, this product may enhance the effect of blood pressure rise after clonidine withdrawal. Therefore, patients who stop clonidine within a few days before surgery should use this product with caution. 7. When combined with sympathetic stimulant epinephrine, attention should be paid to the increase of blood pressure due to vasoconstriction. 8. When cholinesterase inhibitors such as neostigmine, annetigmine, and phenolchloride are combined with this product, cholinesterase inhibitors can inhibit the metabolism of this product, enhance the effect of this product and extend the action time, need to reduce the amount with caution. 9. Combined with fentanyl citrate and propofol, it can enhance the effect of this product to slow down the heart beat, and pay attention to reduce the amount with caution. 10. Procaine, succinylcholine combined with this product can prolong the action time of this product and need to be reduced with caution. |
| adverse reactions | the incidence of adverse reactions of this product is 15, 6%. Serious adverse reactions were shock, I .e. excessive reduction of blood pressure, with an incidence of 0.02%. Once it appears, the drug must be stopped immediately and treated appropriately. The main adverse reaction was blood pressure drop, with an incidence of more than 10%. Other adverse reactions include bradycardia, ST segment decline, pulmonary artery pressure rise, asthma, hypoxemia, leukocytosis, total bilirubin rise, A LT(GPT) rise, AST(GOT) rise and LDH rise, the incidence rate is less than 1%. |
Last Update：2024-04-09 02:00:07
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Product Name: Landiolol hydrochloride Visit Supplier Webpage Request for quotationCAS: 144481-98-1
Tel: 0714-3999186
Email: 2853786052@qq.com
Mobile: 86+15671228036
QQ: 2853786052
Wechat: 15671228036
Product Name: Landiolol hydrochloride Visit Supplier Webpage Request for quotation
CAS: 144481-98-1
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
CAS: 144481-98-1
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
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