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

• ChemBase ID: 276
• Molecular Formular: C21H26N2O7
• Molecular Mass: 418.44034
• Monoisotopic Mass: 418.17400118
• SMILES: O(C(=O)C1=C(NC(=C(C1c1cc([N+](=O)[O-])ccc1)C(=O)OCCOC)C)C)C(C)C
• Canonical SMILES: COCCOC(=O)C1=C(C)NC(=C(C1c1cccc(c1)[N+](=O)[O-])C(=O)OC(C)C)C
• 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

NAMES AND DATABASE IDS

Names

• IUPAC name: 3-(2-methoxyethyl) 5-propan-2-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• 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: Nimotop; Periplum
• Synonyms: 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic Acid 3-(2-Methoxyethyl) 5-(1-Methylethyl) Ester; (+/-)-Nimodipine; Admon; Nimodipine AP; Nimotop; Periplum; Nimotop; Isopropyl 2-methoxyethyl 1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate; Nimodipine; Nimodipino [INN-Spanish]; Nimodipinum [INN-Latin]; Nimodipine; Isopropyl 2-methoxyethyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate; 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester; 3-isopropyl 5-(2-methoxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate; Bay-E 9736; 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid; 2-Methoxyethyl-1-methylethyl ester; Calnit; Kenesil; 3-(2-methoxyethyl) 5-propan-2-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate

Database IDs

• CAS Number: 66085-59-4
• EC Number: 266-127-0
• MDL Number: MFCD00153848
• PubChem SID: 160963739; 24277858; 46508497
• PubChem CID: 4497

CALCULATED PROPERTIES

JChem

• H Acceptors: 6
• H Donor: 1
• LogD (pH = 5.5): 2.2858284
• LogD (pH = 7.4): 2.5375297
• Log P: 2.5419018
• Molar Refractivity: 112.3756 cm^3
• Polarizability: 42.033375 Å^3
• Polar Surface Area: 119.68 Å^2
• Rotatable Bonds: 10
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.41
• LOG S: -4.54
• Solubility (Water): 1.20e-02 g/l

PROPERTIES

Physical Property

• Solubility: 45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin: insoluble; Chloroform; H2O: insoluble; Methanol; methanol: soluble62.5 mg/mL
• Apperance: Pale Yellow Solid; white solid
• Melting Point: 116-121°C
• Hydrophobicity(logP): 2.7; 4.144

Safety Information

• Storage Condition: -20°C; -20°C Freezer; Room Temperature (15-30°C), Protect from light
• Storage Warning: IRRITANT
• RTECS: US7975500
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 1
• Risk Statements: 48/22
• TSCA Listed: false
• GHS Pictograms: GHS08
• GHS Signal Word: Warning
• GHS Hazard statements: H373
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves

Pharmacology Properties

• Gene Information: human ... ADORA3(140), CACNG1(786)rat ... Adora1(29290), Adora2a(25369)
• Mechanism of Action: Blocks intracellular influx of calcium that is thought to be a central to ischaemic neuronal damage.; Calcium channel blockader; Nimodipine binds specifically to L-type voltage-gated calcium channels

Product Information

• Purity: 95%
• Salt Data: Free Base
• Application(s): Cerebral vasodilator

DETAILS

MP Biomedicals - 02159803

Potent calcium channel antagonist.

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]

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.

Toronto Research Chemicals - N478200

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

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• 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
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