3α-(Acetyloxy)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2α-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one
diltiazem
CAS: 42399-41-7
Molecular Formula: C22H26N2O4S
3α-(Acetyloxy)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2α-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one - Names and Identifiers
3α-(Acetyloxy)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2α-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one - Physico-chemical Properties
| Molecular Formula | C22H26N2O4S |
| Molar Mass | 414.52 |
| Density | 1.26±0.1 g/cm3(Predicted) |
| Melting Point | 212 °C (decomp) |
| Boling Point | 594.4±50.0 °C(Predicted) |
| Solubility | Chloroform (Slightly), DMSO (Slightly), Methanol (Slightly) |
| Appearance | Solid |
| Color | White to Off-White |
| pKa | pKa 7.70 (Uncertain) |
| Storage Condition | -20°C Freezer |
3α-(Acetyloxy)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2α-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one - Reference Information
| NIST chemical information | Information provided by: webbook.nist.gov (external link) |
| EPA chemical information | Information provided by: ofmpub.epa.gov (external link) |
| background introduction | calcium antagonists have achieved many achievements in clinical treatment of coronary heart disease, hypertension, angina pectoris, arrhythmia and other cardiovascular diseases. Diltiazem is a representative drug of non-dihydropyridine calcium antagonists. Its cardiovascular effect is between aniline and dihydropyridine. It has a mild peripheral vasodilator effect and can increase Coronary and renal blood flow has been widely used in the treatment of ischemic heart disease and hypertension. Numerous clinical studies have been conducted on its effectiveness in Japan, Europe and the United States. Diltiazem acts on the vascular smooth muscle and atrioventricular node of coronary blood vessels and peripheral blood vessels, inhibits the inflow of calcium ions into the cells, showing the effect of vasodilation and prolonging the conduction time of atrioventricular node, thereby affecting hypertension and arrhythmia, Angina pectoris is effective. Diltiazem and other atrioventricular node blockers are currently used as first-line drugs to control room rates in most patients. The mechanism of its treatment of arrhythmia is: by inhibiting the influx of calcium ions, the slope of the 4-phase automatic depolarization is reduced, which inhibits the sinus node and atrioventricular node autonomously inhibits the conductivity of the atrioventricular node, but has no obvious inhibitory effect on the atrioventricular bypass; Inhibit suaventricular rapid arrhythmia caused by atrial electrical stimulation; in addition, there are vasodilation and mild negative inotropic effects. In addition, diltiazem is as effective as diuretics, β-receptor antagonists or diuretics plus β-receptor antagonists in preventing stroke, myocardial infarction and other cardiovascular deaths. Diltiazem is more effective than dihydropyridine calcium antagonists in reducing cardiovascular complications. Its possible mechanism is its function of reversing left ventricular hypertrophy; diltiazem has lower sympathetic excitability than dihydropyridine calcium antagonists, and there is no leg swelling and blush that dihydropyridine calcium antagonists often have complications such. Compared with thiazide diuretics and β-receptor antagonists, diltiazem has no significant difference in total mortality and incidence of major cardiovascular events. |
| overview | calcium antagonists have achieved many results in clinical treatment of coronary heart disease, hypertension, angina pectoris, arrhythmia and other cardiovascular diseases. Diltiazem is a representative drug of non-dihydropyridine calcium antagonists. Its cardiovascular effect is between aniline and dihydropyridine. It has a mild peripheral vasodilator effect and can increase Coronary and renal blood flow has been widely used in the treatment of ischemic heart disease and hypertension. Numerous clinical studies have been conducted on its effectiveness in Japan, Europe and the United States. Diltiazem acts on the vascular smooth muscle and atrioventricular node of coronary blood vessels and peripheral blood vessels, inhibits the inflow of calcium ions into the cells, showing the effect of vasodilation and prolonging the conduction time of atrioventricular node, thereby affecting hypertension and arrhythmia, Angina pectoris is effective. Diltiazem and other atrioventricular node blockers are currently used as first-line drugs to control room rates in most patients. The mechanism of its treatment of arrhythmia is: by inhibiting the influx of calcium ions, the slope of the 4-phase automatic depolarization is reduced, which inhibits the sinus node and atrioventricular node autonomously inhibits the conductivity of the atrioventricular node, but has no obvious inhibitory effect on the atrioventricular bypass; Inhibit suaventricular rapid arrhythmia caused by atrial electrical stimulation; in addition, there are vasodilation and mild negative inotropic effects. In addition, diltiazem is as effective as diuretics, β-receptor antagonists or diuretics plus β-receptor antagonists in preventing stroke, myocardial infarction and other cardiovascular deaths. Diltiazem is more effective than dihydropyridine calcium antagonists in reducing cardiovascular complications. Its possible mechanism is its function of reversing left ventricular hypertrophy; diltiazem has lower sympathetic excitability than dihydropyridine calcium antagonists, and there is no leg swelling and blush that dihydropyridine calcium antagonists often have complications such. Compared with thiazide diuretics and β-receptor antagonists, diltiazem has no significant difference in total mortality and incidence of major cardiovascular events. As a representative drug of non-dihydropyridine calcium channel blockers, diltiazem can bind to slow calcium channels in the action potential 2 phase to prevent calcium ions from flowing into the cell and significantly dilate coronary arteries and peripheral blood vessels. Diltiazem can also block potassium ion outflow and sodium ion inflow, and prolong the effective refractory period of the atrioventricular node. It has a strong dilation effect on arterial blood vessels, reduces peripheral vascular resistance and thus produces a significant blood pressure reduction effect, which can eliminate coronary vasospasm, increase coronary blood supply, and improve myocardial blood supply. In addition, it has a certain inhibitory effect on catecholamines, acetylcholine, histamine and other vasoactive substances and platelets. Diltiazem as a selective non-dihydropyridine calcium channel blocker. It has a wide range of applications in the treatment of cardiovascular diseases and has a significant effect. By inhibiting the flow of calcium ions into peripheral blood vessels, coronary vascular smooth muscle cells and atrioventricular node cells, it can dilate blood vessels and relax the smooth muscle of peripheral arterial blood vessels, so that peripheral vascular resistance is reduced and its antihypertensive effect is exerted. It can be used clinically for various properties Hypertension is especially suitable for patients with hypertensive emergencies complicated with arrhythmia and angina pectoris. Calcium channel block has a preventive effect on ischemic acute renal failure, and has a certain protective effect on the kidney in patients with hypertension. The disadvantage is that the bioavailability of diltiazem oral preparations is relatively low, and the blood concentration peaks for a long time. Therefore, diltiazem oral preparations are mainly used clinically for the treatment of patients with mild hypertension and variant angina. When diltiazem is used in the treatment of hypertension, the drug is required to take effect quickly and achieve the purpose of treatment in a short time, so as to ensure that the damage of the target organ of the patient is minimized. And the duration is short, and the effect disappears quickly after stopping the drug. Therefore, intravenous medication should be the first choice, and intravenous medication can be precisely regulated. |
| pharmacological action | diltiazem is a calcium channel blocker, which can relieve angina pectoris, reduce blood pressure, have negative inotropic effect, and slow down the conduction of sinoatrial node and atrioventricular node. |
| Synthetic route | Ethyl-p-methoxy (I) reacts with N-bromosuccinimide in acetone to produce racemic eryriobromol (II),(II) esterified with butyrate anhydride to produce racemic bromine ester (III). (III) Lipase kinetic resolution using Candida cylindracea to generate (S,S)-enantiomers, enantioselective hydrolysis to generate chiral bromools (V),(V) adding NaOMe to generate epoxide (VI). (VI) Condensation with 2-aminothiophenol (VII) to form the final product diltiazem (VIII). The specific reaction process is as follows: |
| indications | can be used to treat supraventricular arrhythmia, angina pectoris and hypertension in the elderly |
| specification | hydrochloride powder for injection: 10mg,50mg each. pH(5mg/mL):3.7~4.1 |
| usage and dosage | usage and dosage: tablets, 30-60 mg each time, 3 times a day, intravenous injection: 10mg for the first time, or calculated at 0.15-0.25 mg/kg, dissolved and diluted with 5-10mL of sodium chloride or glucose injection before use, and slowly injected within 3min, it can be repeated after 15min, or intravenous drip according to body weight of 5~15 μ g/(kg min) suitable solvent: intravenous injection: 10mg dissolved in water for injection or 5mL of 0.9% sodium chloride or 5% glucose injection; Intravenous drip: 10~50mg diluted with 5% ~ 10% glucose injection 250~500mL. delivery speed: intravenous injection: 1~3min; Intravenous drip: 1~4h, drip speed 5~15 μ g/(kg min). |
| stability | powder injection for injection should be stored at room temperature with controlled temperature and should be avoided from freezing. The prepared injection remained stable within 24 hours at room temperature. PVC has adsorption effect on this product, which will cause the loss of this product, especially when the pH value is neutral or alkaline. |
| adverse reactions | the most common adverse reactions are edema, headache, nausea, dizziness, rash, weakness, etc. Acute liver damage is rare when this product is applied |
| drug interaction | and β-adrenergic receptor blockers should be avoided at the same time or within a similar time |
| precautions | 1. the safety and effectiveness of this product for children have not been determined. The metabolism of this product in the liver is excreted by the kidney and bile. Long-term administration should be regularly monitored in the laboratory 2. Sinus bradycardia, atrioventricular block above degree II, cardiac insufficiency are contraindicated, pregnant women and those who are allergic to this drug are contraindicated, and I degree atrioventricular block, lactation women should use it with caution. 3. Intravenous injection is only used for supraventricular tachycardia and rapid atrial fibrillation, and should be performed under ECG monitoring. 4. This product is forbidden to be used with β-blockers. 5. This product should be swallowed with sustained-release tablets |
| contraindications | pregnant women and sick sinus syndrome, ventricular tachycardia, severe heart failure, Ⅱ or Ⅲ degree atrioventricular block (except for ventricular pacemaker), blood pressure <90mmHg, patients with acute myocardial infarction and pulmonary congestion and those who are allergic to this product are prohibited, and injections containing benzyl alcohol are prohibited for newborns. Use with caution in patients with impaired liver and kidney function. |
| diagnosis points | poisoning manifestations: 1. bradycardia, heart rate <40 beats/min, sinus arrest, Ⅲ ° atrioventricular block. 2. aggravate or induce cardiac insufficiency, heart failure, pulmonary edema can be fatal. 3. Syncope, lethargy, coma. 4. Jaundice, hepatomegaly, elevated serum transaminase. 5. Leukopenia, thrombocytopenia. 6. exfoliative dermatitis, abscess dermatitis. |
| treatment principle | 1. when taking a large amount by mistake, it will immediately induce vomiting, gastric lavage and catharsis. 2. 10% 10ml of calcium chloride is added into 20ml of glucose solution, slowly injected intravenously, then 20-50 mg/kg should be given continuously intravenously every hour, and blood calcium should be measured 30 minutes after medication and every 2 hours to maintain the blood calcium concentration at 2mmol/L. 3. When bradycardia or high atrioventricular block, use atropine and isoproterenol; install a temporary pacemaker if necessary. 4. For patients with cardiac insufficiency, the infusion speed should be limited, and isoproterenol, dopamine, dobutamine and diuretics can be used. 5. Hypotension, dopamine or norepinephrine can be given. 6. other symptomatic treatment |
| introduction of related drugs | amiodarone: amiodarone, whose English name is Cordarone, is currently the most widely used antiarrhythmic drug. it is a class iii multi-channel blocker that can terminate various supraventricular and ventricular tachyarrhythmias, and is effective for increased self-discipline, triggering activity or reentry agitation. Because of its small arrhythmia effect, does not affect indoor conduction, no negative inotropic response, does not increase the pacing threshold, and has a good anti-fibrillation effect, it is mainly used for various organic heart diseases and acute coronary syndromes, Myocardial hypertrophy, left ventricular dysfunction, and anti-rapid arrhythmia in intraventricular block. Amiodarone can be used as the first-line treatment of symptomatic atrial fibrillation with left ventricular dysfunction or chronic heart failure. It can be used for malignant arrhythmia leading to cardiac arrest and hemodynamically stable ventricular tachycardia. In addition, it can also be used as an auxiliary drug for ICD to reduce the number of discharges. Prophylactic use of amiodarone in perioperative cardiac surgery. Amiodarone combined with β-blockers can effectively control electrical storms. Amiodarone is an iodine-containing compound with furan structure. Therefore, chronic application can induce hypothyroidism or hyperthyroidism, and can also cause extracardiac side effects such as pulmonary fibrosis. Therefore, indications should be strictly controlled and follow-up should be strengthened in application. Hypotension, bradycardia, and phlebitis may occur in acute intravenous application, so ECG and blood pressure monitoring are required, and large intravenous drip is selected. |
| main reference materials | [1] Liu Yuhua et al. Clinical effects of diltiazem. Chinese Journal of Traditional Chinese and Western Medicine, No. 16, 2004. [2] Peak. Clinical observation of diltiazem in the treatment of hypertensive emergencies. Journal of Integrated Traditional Chinese and Western Medicine Cardiovascular Diseases. 2011,9(3):376-377. [3] Editor-in-Chief Tang Jingbo. Safe application and compatibility of 452 injections. Zhengzhou: Henan Science and Technology Press. 2014. [4]McCague, R.; Wang, S.; Taylor, S.J.C. (Celltech Group plc); Chiral arylpropionates and their use. WO 9413828. [5] Liu Zhancai editor-in-chief. Practical Poisoning First Aid Digital Manual. Tianjin: Tianjin Science and Technology Press. 2009. [6] edited by Xuan Yupeng. Encyclopedia of Coronary Heart Disease. Xi'an: Shaanxi Science and Technology Press. 2010. Page 190. [7] Heart Rhythm Branch of Chinese Society of Biomedical Engineering, Cardiovascular Branch of Chinese Medical Association, Working Group on Application Guidelines for Amiodarone Antiarrhythmic Therapy. Application Guidelines for Amiodarone Antiarrhythmic Therapy (2008). Chinese Journal of Cardiac Pacing and Electrophysiology, 2008,22(5):377-385. |
| use | pharmaceutical intermediates |
| toxic substance data | information provided by: pubchem.ncbi.nlm.nih.gov (external link) |
Last Update：2024-04-10 22:29:15
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