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

General Information

Structure

Molecular Formula

C₂₁H₂₆N₂O₇

Molecular Mass

418.44034

Exact Mass

418.17400118

Charge

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

Calculated Properties

JChem

LogD (pH = 7.4)

2.54

LogD (pH = 5.5)

2.54

Log P

2.54

Rotatable Bonds

H Donor

H Acceptors

Lipinski's Rule of Five

true

Acid pKa

16.96

Polar Surface Area

117.00

Polarizability

43.47

Molar Refractivity

111.37

LOG S

-3.29

Data Source

Names and Identifiers

IUPAC name

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

Synonyms

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 Traditional name

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

Brand Name

NimotopPeriplum

API Name

Nimodipine

International Nonproprietary Name (INN)

nimodipinumnimodipinenimodipino

Names and Identifiers

Registration numbers

MDL Number

MFCD00153848

CAS Number

66085-59-4

PubChem SID

2427785816096373946508497135610175

EC Number

266-127-0

PubChem CID

4497

DrugBank ID

DB00393

Drug Central Database

1,937

MetaboLights Database

MTBLS2291MTBLS2145MTBLS3950MTBLS2349MTBLS1071MTBLS804MTBLS1642MTBLS673MTBLS3750

LINCS Database

CHEBI ID

ACToR Database

KEGG ID

PubMed Citation Links

8519001218694512230091422262041121376061618036217110283

Wikipedia Title

Nimodipine

Reactom Database

R-HSA-9614031R-HSA-9725855

CompTox Database

SureChEMBL Database

KEGG DRUG Database

Reaxys Registry

Patent number

CHEMBL

BindingDB Database

Registration numbers

Properties

Product Information

Pharmacology Properties

Gene Information

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

Mechanism of Action

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.

Properties

Related Proteins

No Data Available

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Molecular Spectra

No Data Available

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Molecule Details

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.

Molecule Details

References

PubChem Literature

From Data Sources

• 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)

• Martindale, The Extra Pharmacopoeia, 31st edn., Pharmaceutical Press, 1996, 922

• Meyer, H. et al., Arzneim.-Forsch., 1981, 31, 407; 1982, 32, 338; 1983, 33, 106, (synth, pharmacol, enantiomers)

• Schchtele, C. et al., Naunyn-Schmiedeberg's Arch. Pharmacol., 1987, 335, 340, (pharmacol)

• Negwer, M., Organic-Chemical Drugs and their Synonyms, 7th edn., Akademie-Verlag, 1994, 8483, (synonyms)

• Ger. Pat., 1981, Bayer, 2 935 451; CA, 95, 42922j, (synth, resoln)

• U.K. Pat., 1979, Bayer, 2 018 134; CA, 92, 220691r, (synth, pharmacol)

• Nimodipine, (Eds. Scriabine, A. et al), Springer-Verlag, 1991, (book)

• Wadworth, A.N. et al., Drugs Aging, 1992, 2, 262, (rev)

References

Bioactivity

PubChem BioAssay

Bioactivity