Huagongshe화공사 화학 정보 인쇄 보고서 · 연구 참고용
딜티아젬
딜티아젬 · DILTIAZEN · Dilthiazem · (2S,3S)-5-(2-(diMethylaMino)ethyl)-2-(4-Methoxyphenyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepin-3-yl acetate · Coras · NSC7324 · NSC 7324 · NSC-7324
식별자 및 물리적 특성
| CAS No. | 42399-41-7 |
|---|---|
| 분자식 | C22H26N2O4S |
| 평균 분자량 | 414.5 g/mol |
| 단동위원소 질량 | 414.16132831 g/mol |
| SMILES | COc1ccc([C@@H]2Sc3ccccc3N(CCN(C)C)C(=O)[C@@H]2OC(C)=O)cc1 |
| InChIKey | HSUGRBWQSSZJOP-RTWAWAEBSA-N |
| PubChem CID | 39186 |
| ChEMBL | CHEMBL23 |
| ChEBI | CHEBI:101278 |
| EC No. | 255-796-4 |
| DTXSID | DTXSID9022940 |
| 현지명 | 딜티아젬 |
화학 및 물리적 성질
| XLogP | 3.1 |
|---|---|
| 극성 표면적 | 84.4 |
| 수소 결합 공여자 수 | 0 |
| 수소 결합 수용자 수 | 6 |
| 회전 가능 결합 수 | 7 |
| 무거운 원자 수 | 29 |
| 형식 전하 | 0 |
| 복잡도 | 565 |
| 물질 분류 | Pharmaceutical |
| 의약품 | PharmaceuticalPharmaceuticals -> Used in SwitzerlandPharmaceuticals -> Listed in ZINC15 |
| LogP(분배 계수) | log Kow = 2.702.82.93 |
| Color/Form | White crystalline powder |
| 용해도 | Soluble in methanol or chloroformIn water, 465 mg/l @ 25 °C1.68e-02 g/L클로로포름(약간 용해됨), DMSO(약간 용해됨), 메탄올(약간 용해됨) |
| Human Drugs | Breast FeedingLactationMilk, HumanAntihypertensive AgentsCalcium Channel BlockersAntiarrhythmicsVasodilator AgentsPharmaceuticals |
| 끓는 점 | Decomposes594.4±50.0 °C(Predicted) |
| 녹는점 | 187-188212 °C (decomposes)231 °C212 °C (decomp) |
| Optical Rotation | Mol wt 450.99. Fine needles from ethanol-isopropanol, mp 207.5-212 °C. Odorless, with a bitter taste. Specific optical rotation at 24 °C for D (sodium) line = +98.3 plus or minus 1.4 deg (c = 1.002 in methanol). Freely soluble in water, methanol, chloroform, formic acid. Slightly soluble in absolute ethanol. Practically insoluble in benzene. Insoluble in ether /Hydrochloride/ |
| Physical Description | Solid |
| Stability/Shelf Life | Intact vials should be stored under refrigeration and protected from freezing. Diltiazem HCl may be stored for up to one month at room temp but should then be destroyed. /Diltiazem HCl/The photostability of diltiazem was studied in aq solns at different pH values. Firstly, the hydrolysis of the drug to desacetyldiltiazem in alkaline medium was evaluated and then the drug photodegradation under exposure to UVA-UVB radiation (solar simulator) was monitored by HPLC methods. The main photoproduct was isolated and characterized as diltiazem-S-oxide on the basis of the NMR and mass spectra. The HPLC method was also applied to the selective analysis of diltiazem in commercial formulations. Tests on mutagenicity and photomutagenicity of the drug were also carried out using Salmonella typhimurium TA 102 strain. In this testing the drug neither was mutagenic nor toxic. |
| Dissociation Constants | 8.028.06pKa = 8.06 |
| 밀도 | 1.26±0.1 g/cm3(Predicted) |
| 저장 조건 | -20°C Freezer |
| 물리적 상태 | 고체 |
| pKa(산도 계수) | pKa 7.70 (Uncertain) |
| 색상 | 흰색에서 황백색까지 |
| NIST | Diltiazem(42399-41-7) |
| EPA | 1,5-Benzothiazepin-4(5H)-one, 3-(acetyloxy)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-, (2S,3S)- (42399-41-7) |
안전 및 규제
| 규제 정보 | Diltiazem: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right. |
|---|---|
| 기타 안전 정보 | IMAP assessments - 1,5-Benzothiazepin-4(5H)-one, 3-(acetyloxy)-5-[2-(dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-, (2S-cis)-: Environment tier I assessment |
| FDA 요건 | The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl diltiazem hydrochloride and diltiazem maleate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Diltiazem hydrochloride, diltiazem maleate/ |
| 보관 조건 | Diltiazem hydrochloride tablets should be stored in tight, light-resistant, and extended-release capsules in tight containers at 15-30 °C, unless otherwise specified by the manufacturer. /Diltiazem hydrochloride/Extended-release tablets containing diltiazem malate alone or in fixed combination with enalapril maleate should be stored in well-closed containers at 15-30 °C. /Diltiazem malate/Diltiazem hydrochloride injection in vials should be refrigerated at 2-8 °Cfreezing of the injection should be avoided. Diltiazem hydrochloride injection may be stored at room temp for up to 1 monthafter that time, the injection should be discarded. Diltiazem hydrochloride powder for injection in single-use vials ... or in single-use syringes ... should be stored at a room temp of 15-30 °Cfreezing of the powder for injection should be avoided. Following reconstitution of diltiazem hydrochloride powder for injection from single-dose vials and transferred to polyvinyl chloride (PVC) bags ... or after actuation of the single-use syringe, the reconstituted solns of diltiazem hydrochloride are stable for 24 hr at controlled room tempunused portions of reconstituted soln in the PVC bags or single-use syringes should be discarded after this period. /Diltiazem hydrochloride/ |
| 처리 방법 | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
| 체내 부담 | A 15-yr-old woman was admitted to the ICU after ... auto-intoxication with 10 tablets of 200 mg diltiazem sustained release. ... Max plasma lactate concn was 10 mmol/l and the highest measured plasma diltiazem level was 500 micrograms/l. |
| Treatment | In the event of overdose or exaggerated response, appropriate supportive measures should be employed in addition to gastrointestinal decontamination. If bradycardia and/or high-degree AV block occurs, administer atropine (0.60 to 1.0 mg). If there is no response to vagal blockage, administer isoproterenol cautiously. Fixed high-degree AV block should be treated with cardiac pacing. In cases of cardiac failure, administer inotropic agents (isoproterenol, dopamine, or dobutamine) and diuretics. If hypotension occurs, use vasopressors (e.g. dopamine or levarterenol bitartrate). (L1712) |
| 상호 작용 | Diltiazem interacts with Propranolol reducing oral clearance with increased concns of propanolol by inhibition of first-pass metab. Propanolol dose may need to be reduced. /from table/Diltiazem interacts with cyclosporine increasing cyclosporine concns. Reduce cyclosporine dose after starting... diltiazemmonitor cyclosporine concns. /from table/Diltiazem interacts with disopyramide, flecainide /causing/ cardiac failure by additive depression of myocardial contractility. Avoid use if possible, particularly in patients with impaired myocardial function. /from table/Diltiazem interacts with Amiodarone, flecainide /causing/ sinus arrest, heart block by additive depression of sinus node function & AV nodal conduction. Use combination with extreme caution. /from table/For more Interactions (Complete) data for DILTIAZEM (15 total), please visit the HSDB record page. |
| 건강 영향 | Because of its negative inotropic effect, diltiazem causes a modest decrease in heart muscle contractility and reduces myocardium oxygen consumption. Its negative chronotropic effect results in a modest lowering of heart rate, due to slowing of the sinoatrial node. It results in reduced myocardium oxygen consumption. Because of its negative dromotropic effect, conduction through the AV (atrioventricular) node is slowed, which increases the time needed for each beat. This results in reduced myocardium oxygen consumption. A reflex sympathetic response, caused by the peripheral dilation of vessels and the resulting drop in blood pressure, works to counteract the negative inotropic, chronotropic and dromotropic effects of diltiazem. Undesirable effects include hypotension, bradycardia, dizziness, and flushing. (Wikipedia) |
| Hepatotoxicity | Diltiazem therapy is associated with a low rate of mild and transient elevations in serum aminotransferase levels which are usually asymptomatic and often resolve even with continuation of therapy. Clinically apparent, acute liver injury with jaundice due to diltiazem is rare and only isolated case reports have been published. In large case series of drug induced liver injury, calcium channel blockers are rarely mentioned. Most cases attributed to diltiazem have been marked by a short latency period (3 to 14 days) and features of hypersensitivity with fever, rash and eosinophilia. The pattern of liver injury was ranged from cholestatic to hepatocellular. Jaundice is often absent and usually mild. Autoantibody formation has not been described. Thus, liver injury from diltiazem is likely to be idiosyncratic in nature and is typically mild and self-limited with resolution within 4 to 8 weeks of stopping. Acute hepatic injury is listened as a possible adverse event in the diltiazem product label. |
| 유해 작용 | * Common adverse effects of diltiazem therapy include peripheral edema, bradycardia, dizziness, headache, and fatigue. |
| 노출 경로 | Intravenous, Oral. Diltiazem is well absorbed from the gastrointestinal tract but undergoes substantial hepatic first-pass effect. |
| Milk Concentrations | Diltiazem is excreted into human milk. |
| 독성 요약 | Diltiazem is available in many dosage forms and strengths, making it imperative to be cautious when prescribing, dispensing, and administering this medication. There have been reports of diltiazem overdose in amounts ranging from Clinical FeaturesPossibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum, diltiazem, like verapamil, inhibits the influx of extracellular calcium across both the myocardial and vascular smooth muscle cell membranes. The resultant inhibition of the contractile processes of the myocardial smooth muscle cells leads to dilation of the coronary and systemic arteries and improved oxygen delivery to the myocardial tissue. |
| Signs and Symptoms | LD<sub>50</sub>=740mg/kg (orally in mice) |
| Ongoing Test Status | The following link will take the user to the National Toxicology Program (NTP) Test Agent Search Results page, which tabulates all of the "Standard Toxicology & Carcinogenesis Studies", "Developmental Studies", and "Genetic Toxicity Studies" performed with this chemical. Clicking on the "Testing Status" link will take the user to the status (i.e., in review, in progress, in preparation, on test, completed, etc.) and results of all the studies that the NTP has done on this chemical. /Diltiazem hydrochloride/ [http://ntp-apps.niehs.nih.gov/ntp_tox/index.cfm?fuseaction=ntpsearch.searchresults&searchterm=33286-22-5] |
| Medical Surveillance | Patients with hemodynamic compromise from calcium channel blocker overdose that does not respond to initial therapy should receive invasive hemodynamic monitoring. Specific cardiac output & systemic vascular resistance measurement may determine the optimal pharmacologic therapy & fluid supplement. /Calcium channel blocker/ |
| 유해 물질 데이터 | 42399-41-7(Hazardous Substances Data) |
용도
용도
Diltiazem is a potent vasodilator compound. Antihypertensive.