CAS 66085-59-4|2-Methoxyethyl-1-methylethyl ester|Nimodipine|3-(2-methoxyethyl) 5-propan-2-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate|Bay-E 9736|1,4-Dihydro-2,6-dimethyl...

基本信息

化学结构

分子式

C₂₁H₂₆N₂O₇

分子量

418.44034

精确质量

418.17400118

电荷

InChI

InChI=1S/C21H26N2O7/c1-12(2)30-21(25)18-14(4)22-13(3)17(20(24)29-10-9-28-5)19(18)15-7-6-8-16(11-15)23(26)27/h6-8,11-12,19,22H,9-10H2,1-5H3

InChIKey

UIAGMCDKSXEBJQ-UHFFFAOYSA-N

Canonic Smiles

COCCOC(=O)C1=C(C)NC(=C(C1c1cccc(c1)[N+](=O)[O-])C(=O)OC(C)C)C

Isomeric Smiles

O(C(=O)C1=C(NC(=C(C1c1cc([N+](=O)[O-])ccc1)C(=O)OCCOC)C)C)C(C)C

计算属性

JChem

LogD (pH = 7.4)

2.54

LogD (pH = 5.5)

2.54

Log P

2.54

可自由旋转的化学键

质子供体

质子受体

里宾斯基五规则

true

Acid pKa

16.96

极化表面积

117.00

极化性

43.47

摩尔折射率

111.37

LOG S

-3.29

数据来源

名称和标识

IUPAC标准名

3-(2-methoxyethyl) 5-propan-2-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

别名

2-Methoxyethyl-1-methylethyl esterNimodipine1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acidBay-E 9736Nimodipinum [INN-Latin]Nimodipino [INN-Spanish] NimotopIsopropyl 2-methoxyethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylateNimodipineIsopropyl 2-methoxyethyl 1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate3-isopropyl 5-(2-methoxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl esterPeriplumNimodipine AP(+/-)-NimodipineAdmon1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic Acid 3-(2-Methoxyethyl) 5-(1-Methylethyl) EsterNimotopCalnit3-(2-methoxyethyl) 5-propan-2-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylateKenesilisopropyl 2-methoxyethyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylatenimodipineBAY e 9736isopropyl 2-methoxyethyl 1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate2,6-dimethyl-4-(3'-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-beta-methoxyethyl ester 5-isopropyl esterNimodipine

IUPAC传统名

nimodipine 3-(2-methoxyethyl) 5-propan-2-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

商标名

NimotopPeriplum

API名称

Nimodipine

国际非专利药品(INN)

nimodipinumnimodipinenimodipino

名称和标识

数据登录号

MDL号

MFCD00153848

CAS号

66085-59-4

PubChem SID

2427785816096373946508497135610175

EC号

PubChem CID

DrugBank ID

CHEBI ID

KEGG ID

ACToR数据库

MetaboLights数据库

MTBLS2291MTBLS3950MTBLS2145MTBLS804MTBLS2349MTBLS1071MTBLS673MTBLS1642MTBLS3750

Drug Central Database

1,937

PubMed文献链接

8519001218694512230091412137606222620411711028316180362

LINCS数据库

LSM-1659

维基百科标题

Nimodipine

Reactom Database

R-HSA-9614031R-HSA-9725855

SureChEMBL数据库

CompTox数据库

Reaxys Registry

KEGG DRUG Database

专利号

BindingDB数据库

CHEMBL

数据登录号

化合物性质

药理学性质

相关基因信息

human ... ADORA3(140), CACNG1(786)rat ... Adora1(29290), Adora2a(25369)

生物活性机理

Calcium channel blockader

Nimodipine binds specifically to L-type voltage-gated calcium channels

Blocks intracellular influx of calcium that is thought to be a central to ischaemic neuronal damage.

化合物性质

分子相关蛋白质

暂无数据

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分子图谱

暂无数据

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描述信息

DrugBank

DB00393

Drug Groups

approved

Description

Nimodipine is a 1,4-dihydropyridine calcium channel blocker. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, nimodipine prevents calcium-dependent smooth muscle contraction and subsequent vasoconstriction. Compared to other calcium channel blocking agents, nimodipine exhibits greater effects on cerebral circulation than on peripheral circulation. Nimodipine is used to as an adjunct to improve the neurologic outcome following subarachnoid hemorrhage from ruptured intracranial aneurysm.

Indication

For use as an adjunct to improve neurologic outcome following subarachnoid hemorrhage (SAH) from ruptured intracranial berry aneurysms by reducing the incidence and severity of ischemic deficits.

Pharmacology

Nimodipine belongs to the class of pharmacological agents known as calcium channel blockers. Nimodipine is indicated for the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage from ruptured congenital aneurysms who are in good neurological condition post-ictus (e.g., Hunt and Hess Grades I-III). The contractile processes of smooth muscle cells are dependent upon calcium ions, which enter these cells during depolarization as slow ionic transmembrane currents. Nimodipine inhibits calcium ion transfer into these cells and thus inhibits contractions of vascular smooth muscle. In animal experiments, nimodipine had a greater effect on cerebral arteries than on arteries elsewhere in the body perhaps because it is highly lipophilic, allowing it to cross the blood brain barrier.

Toxicity

Symptoms of overdosage would be expected to be related to cardiovascular effects such as excessive peripheral vasodilation with marked systemic hypotension.

Affected Organisms

Humans and other mammals

Biotransformation

Hepatic metabolism via cytochrome P450 3A4.

Absorption

Bioavailability is 100% following intravenous administration and 3-30% following oral administration due to extensive first-pass metabolism.

Half Life

1.7-9 hours

Protein Binding

95%

References

• Janjua N, Mayer SA: Cerebral vasospasm after subarachnoid hemorrhage. Curr Opin Crit Care. 2003 Apr;9(2):113-9. [Pubmed]

• Allen GS, Ahn HS, Preziosi TJ, Battye R, Boone SC, Boone SC, Chou SN, Kelly DL, Weir BK, Crabbe RA, Lavik PJ, Rosenbloom SB, Dorsey FC, Ingram CR, Mellits DE, Bertsch LA, Boisvert DP, Hundley MB, Johnson RK, Strom JA, Transou CR: Cerebral arterial spasm--a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med. 1983 Mar 17;308(11):619-24. [Pubmed]

• Belfort MA, Anthony J, Saade GR, Allen JC Jr: A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia. N Engl J Med. 2003 Jan 23;348(4):304-11. # [Pubmed]

• Kim JH, Park IS, Park KB, Kang DH, Hwang SH: Intraarterial nimodipine infusion to treat symptomatic cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Korean Neurosurg Soc. 2009 Sep;46(3):239-44. Epub 2009 Sep 30. [Pubmed]

• Tomassoni D, Lanari A, Silvestrelli G, Traini E, Amenta F: Nimodipine and its use in cerebrovascular disease: evidence from recent preclinical and controlled clinical studies. Clin Exp Hypertens. 2008 Nov;30(8):744-66. [Pubmed]

• Vergouwen MD, Vermeulen M, Roos YB: Effect of nimodipine on outcome in patients with traumatic subarachnoid haemorrhage: a systematic review. Lancet Neurol. 2006 Dec;5(12):1029-32. [Pubmed]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Selleck Chemicals

S1747

Research Area: Cardiovascular Disease
Biological Activity:
Nimodipine(Nimotop) is a dihydropyridine derivative and an analogue of the calcium channel blocker nifedipine, with antihypertensive activity. Nimodipine inhibits the transmembrane influx of calcium ions in response to depolarization in smooth muscle cells, thereby inhibiting vascular smooth muscle contraction and inducing vasodilatation. Nimodipine has a greater effect on cerebral arteries than on peripheral smooth muscle cells and myocardial cells, probably because this agent can cross the blood brain barrier due to its lipophilic nature. Furthermore, this agent also inhibits the drug efflux pump P-glycoprotein, which is overexpressed in some multi-drug resistant tumors, and may improve the efficacy of some antineoplastic agents. [1, 2]

MP Biomedicals

02159803

Potent calcium channel antagonist.

Sigma Aldrich

N149

Biochem/physiol Actions
Potent L-type Ca2+ channel antagonist.
Caution
Photosensitive
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. N149.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

TRC

N478200

A dihydropyridine calcium channel blocker. It is used as a vasodilator (cerebral).

ChEBI

CHEBI:7575

A dihydropyridine that is 1,4-dihydropyridine which is substituted by methyl groups at positions 2 and 6, a (2-methoxyethoxy)carbonyl group at position 3, a m-nitrophenyl group at position 4, and an isopropoxycarbonyl group at position 5. An L-type calcium channel blocker, it acts particularly on cerebral circulation, and is used both orally and intravenously for the prevention and treatment of subarachnoid hemorrhage from ruptured intracranial aneurysm.

描述信息

参考文献

PubChem文献

数据源提供

• Belfort MA, Anthony J, Saade GR, Allen JC Jr: A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia. N Engl J Med. 2003 Jan 23;348(4):304-11. Pubmed#

• Vergouwen MD, Vermeulen M, Roos YB: Effect of nimodipine on outcome in patients with traumatic subarachnoid haemorrhage: a systematic review. Lancet Neurol. 2006 Dec;5(12):1029-32. Pubmed

• Janjua N, Mayer SA: Cerebral vasospasm after subarachnoid hemorrhage. Curr Opin Crit Care. 2003 Apr;9(2):113-9. Pubmed

• Kappelle, et al., Brit. J. Pharm. , 111 : 887 (1994).

• Allen, G.S., et al.: N. Engl. J. Med., 308, 619 (1983)

• Schluter, H.: Arzneim.-Forsch., 36, 1733 (1983)

• Deyo, R.A., et al.: Science, 243, 809 (1983)

• Bar, P.R. et al., J. Neural Trans. Suppl., 1990, 31, (pharmacol, rev)

• Wang, S.D. et al., Acta Cryst. C, 1989, 45, 1748, (cryst struct)

• Langley, M.S. et al., Drugs, 1989, 37, 669, (rev)

• Lewis, R.J., Sax's Dangerous Properties of Industrial Materials, 8th edn., Van Nostrand Reinhold, 1992, NDY700

• Scriabine, A. et al., Ann. N.Y. Acad. Sci., 1988, 522, 698, (rev, pharmacol)

• Whitfield, P.C. et al., Br. J. Hosp. Med., 1994, 52, 539, (rev)

• Kakarieka, A. et al., J. Neural Trans. Suppl., 1994, 43, 13, (clin trial, rev)