Huagongshe화공사 화학 정보 인쇄 보고서 · 연구 참고용
Nisoldipine
Nisoldipin · 1,4-DIHYDRO-2,6-DIMETHYL-4-(2-NITROPHENYL)-3,5-PYRIDINEDICARBOXYLIC ACID METHYL 2-METHYLPROPYL ESTER · Sular · NisoL · Syseor · SYSCOR · Nisocor · NORVASC
식별자 및 물리적 특성
| CAS No. | 63675-72-9 |
|---|---|
| 분자식 | C20H24N2O6 |
| 평균 분자량 | 388.4 g/mol |
| 단동위원소 질량 | 388.16343649 g/mol |
| SMILES | COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)C)C1c1ccccc1[N+](=O)[O-] |
| InChIKey | VKQFCGNPDRICFG-UHFFFAOYSA-N |
| PubChem CID | 4499 |
| ChEMBL | CHEMBL1726 |
| ChEBI | CHEBI:76917 |
| EC No. | 264-407-7 |
| DTXSID | DTXSID0023371 |
화학 및 물리적 성질
| XLogP | 3.3 |
|---|---|
| 극성 표면적 | 110 |
| 수소 결합 공여자 수 | 1 |
| 수소 결합 수용자 수 | 7 |
| 회전 가능 결합 수 | 7 |
| 무거운 원자 수 | 28 |
| 형식 전하 | 0 |
| 복잡도 | 704 |
| LogP(분배 계수) | 3.263.1 |
| 용해도 | 5.77e-03 g/LDMSO: >10mg/mL |
| Physical Description | Solid |
| Kovats Retention Index | 2679 |
| Collision Cross Section | 195.5 Ų [M+Na]+ [CCS Type: DTBuffer gas: N2Ionization: ESI+Dataset: TOXCASTSource Identifier: DTXSID0023371]190.3 Ų [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards]184.16 Ų [M+H]+ [CCS Type: TW193.15 Ų [M+K]+ [CCS Type: TW187.2 Ų [M+H]+ [CCS Type: TW |
| 녹는점 | 147-148°C |
| 끓는 점 | 503.3±50.0 °C(Predicted) |
| 밀도 | 1.205±0.06 g/cm3(Predicted) |
| 저장 조건 | room temp |
| 물리적 상태 | 가루 |
| pKa(산도 계수) | 2.67±0.70(Predicted) |
| 색상 | 노란색 |
| Merck | 14,6565 |
| InChI | 1S/C20H24N2O6/c1-11(2)10-28-20(24)17-13(4)21-12(3)16(19(23)27-5)18(17)14-8-6-7-9-15(14)22(25)26/h6-9,11,18,21H,10H2,1-5H3 |
| InChIKey | VKQFCGNPDRICFG-UHFFFAOYSA-N |
| SMILES | COC(=O)C1=C(C)NC(C)=C(C1c2ccccc2[N+]([O-])=O)C(=O)OCC(C)C |
| NIST | Nisoldipine(63675-72-9) |
화학적 성질
Nisoldipine D4 is Light Tan Crystals
안전 및 규제
| GHS 분류 | WarningH302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]H312 (60.9%): Harmful in contact with skin [Warning Acute toxicity, dermal]H361 (36.2%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]H411 (34.8%): Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]P203, P264, P270, P273, P280, P301+P317, P302+P352, P317, P318, P321, P330, P362+P364, P391, P405, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 69 reports by companies from 5 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown. For more detailed information, please visit ECHA C&L website. |
|---|---|
| Hazard Classes and Categories | Acute Tox. 4 (100%)Acute Tox. 4 (60.9%)Repr. 2 (36.2%)Aquatic Chronic 2 (34.8%) |
| 유해 작용 | Though nisoldipine is well-tolerated among patients, the drug does have some side effects mainly associated with its vasodilating property. Common adverse effects associated with nisoldipine include flushing, vasodilation (4%), hypotension, syncope, peripheral edema (7% to 29%,dose-related), headache (22%), dizziness (3% to 10%), and nausea (2%).Additionally, adverse reactions such as chest pain (2%), palpitations (3%), dermatitis (2%), pharyngitis (5%), and sinusitis (3%) are reported in patients taking nisoldipine. Occasional adverse effects (less than 1% of the population) include anemia, anxiety, alopecia, dysphagia, and gingival hyperplasia.In less than 1% of the population taking nisoldipine, the following adverse reactions are reported in postmarketing surveillance.Increased blood urea nitrogen, increased creatine phosphokinase, abnormal hepatic function, increased serum creatinine, anorexia, hepatomegaly, abnormal dreams, amnesia, ataxia, cerebral ischemia, cerebrovascular accident, depression, drowsiness, insomnia, abnormal T waves on ECG, ejection murmur (systolic), first-degree atrioventricular block, atrial fibrillation, supraventricular tachycardia, amblyopia, blepharitis, diaphoresis, glaucoma, keratoconjunctivitis, exfoliative dermatitis, facial edema, dermal ulcer, hypersensitivity reaction, maculopapular rash, increased appetite, oral mucosa ulcer, hematuria, colitis, diarrhea, dysgeusia, dyspepsia, dysuria, epistaxis, gastritis, gastrointestinal bleeding, glossitis, leukopenia, malaise, melena, fever, flu-like symptoms, arthralgia, arthritis, gout, bruise, herpes simplex infection, herpes zoster, cellulitis, dyspnea, decreased libido, and gynecomastia is reported by manufacturer's product label.In patients receiving peritoneal dialysis, there is a risk of nisoldipine-associated chyloperitoneum.Withdrawal Effects: Studies have shown that the abrupt withdrawal of nisoldipine may result in chest palpitations, chest pain, or increased severity of angina or hypertension. Thus, the medication must be slowly tapered over time.Drug-Drug Interactions* Nisoldipine is a substrate of the CYP3A4 enzyme. Avoid concurrent use of nisoldipine with cytochrome P450 inducers such as phenytoin. Rifamycins are inducers of cytochrome P450avoid concurrent use with nisoldipine.* Avoid the concurrent use of nisoldipine with cytochrome P450 inhibitors such as itraconazole, as it can increase the serum concentration of nisoldipine and increase the risk of toxicity.* Concurrent administration of calcium channel blockers with dantrolene increases the risk of hyperkalemia.* Nisoldipine has the potential to interact with garlic and turmeric. Nisoldipine acts upon UGT (UDP-glucuronosyltransferase). Garlic and turmeric inhibit UGT, which can increase the serum concentration of nisoldipine. Avoid concurrent administration. |
| 독성 요약 | Toxicity due to nisoldipine is diagnosed based on clinical status and history. As described above, hypotension with reflex tachycardia can occur when patients take excessive doses of dihydropyridine calcium channel blockers such as nisoldipine. In some severe cases of nisoldipine toxicity, the clinician will note hypotension with bradycardia. Secondary findings of confusion, heart failure, and abnormal ECG changes such as PR prolongation can indicate toxicity. Additionally, hyperglycemia in patients without diabetes can suggest calcium channel blockers poisoning.If toxicity is suspected, resuscitation is a priority. IV fluids and atropine for bradycardia are necessary alongside frequent reassessments by clinical staff. If a patient presents with severe symptoms, maintaining the airway, IV isotonic crystalloid, calcium salts, glucagon, insulin, and vasopressor therapy are all viable options. Activated charcoal should be administered to all patients suspected of nisoldipine overdose.Due to high plasma protein binding, dialysis is usually ineffective in nisoldipine overdose. Extracorporeal life support is associated with improved survival in patients with severe CCB poisoning related to cardiac arrest. |
| Drug Induced Liver Injury | Drug Induced Liver Injury Rank (DILIrank 2.0)NisoldipineAmbiguous-DILI-concern3Adverse reactionsDOI:10.1016/j.drudis.2016.02.015 |
| Effects During Pregnancy and Lactation | ◉ Summary of Use during LactationBecause no information is available on the use of nisoldipine during breastfeeding, an alternate drug may be preferred.◉ Effects in Breastfed InfantsRelevant published information was not found as of the revision date.◉ Effects on Lactation and Breastmilk |
| 수질 위해 등급(WGK) | 3 |
| RTECS 번호 | US7975600 |
| 관세 코드 | 2933399090 |
| 위험 문구(R) | 20/21/22 |
| 위험 표시 | Xn |
| 안전 문구(S) | 36 |
| 위험 등급 | Acute Tox. 4 Oral |
| 저장 분류 | 11 - Combustible Solids |
용도
개요
Nisoldipine D4 is another long-acting dihydropyridine calcium channel blocker effective in the treatment of hypertension and angina pectoris. It is reported to have little or no cardiodepressive activity and to be more effective than nifedipine in reducing blood pressure in hypertensives. Nisoldipine has also been shown to be effective in the management of congestive heart failure. Reduction in dosage is necessary in patients with hepatic, but not renal impairment.
용도
Labeled Nisoldipine, intended for use as an internal standard for the quantification of Nisoldipine by GC- or LC-mass spectrometry.
일반 설명
In vitro studies show that the effects ofnisoldipine, 1,4-dihydro-2, 6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinecarboxylic acid methyl 2-methylpropyl ester(Sular), on contractile processes are selective, with greaterpotency on vascular smooth muscle than on cardiac muscle.Nisoldipine is highly metabolized, with five majormetabolites identified. As with most of the dihydropyridines,the cytochrome P450 (CYP) 3A4 isozyme is mainlyresponsible for the metabolism of nisoldipine. The majorbiotransformation pathway appears to involve the hydroxylationof the isobutyl ester side chain. This particular metabolitehas approximately 10% of the activity of the parentcompound.