Nimodipine

Base Information

• Chemical Name: Nimodipine
• CAS No.: 66085-59-4
• Molecular Formula: C21H26N2O7
• Molecular Weight: 418.447
• Hs Code.: 29333990
• European Community (EC) Number: 266-127-0
• NSC Number: 758476
• UNII: 57WA9QZ5WH
• DSSTox Substance ID: DTXSID5023370
• Nikkaji Number: J19.052G
• Wikipedia: Nimodipine
• Wikidata: Q421429
• NCI Thesaurus Code: C692
• RXCUI: 7426
• Pharos Ligand ID: SN94S9QMGKGG
• Metabolomics Workbench ID: 42757
• ChEMBL ID: CHEMBL1428,CHEMBL3197349
• Mol file: 66085-59-4.mol

Synonyms:Admon;Bay e 9736;Bayvit, Nimodipino;Brainal;Calnit;e 9736, Bay;Hexal, Nimodipin;Kenesil;Modus;Nimodipin Hexal;Nimodipin ISIS;Nimodipin-ISIS;Nimodipine;Nimodipino Bayvit;Nimotop;Nymalize;Remontal

Chemical Property of Nimodipine

Chemical Property:

• Appearance/Colour: Crystalline solid
• Vapor Pressure: 3.63E-11mmHg at 25°C
• Melting Point: 125 °C
• Refractive Index: 1.561
• Boiling Point: 534.8 °C at 760 mmHg
• PKA: 2.77±0.70(Predicted)
• Flash Point: 277.3 °C
• PSA: 119.68000
• Density: 1.212 g/cm³
• LogP: 3.82280
• Storage Temp.: Store at RT
• Solubility.: methanol: 62.5 mg/mL
• XLogP3: 3.1
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 9
• Exact Mass: 418.17400117
• Heavy Atom Count: 30
• Complexity: 736

Purity/Quality:

98%99% ^*data from raw suppliers

Nimodipine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 20/21/22-48/22
• Safety Statements: 36

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Cardiovascular Agents
• Canonical SMILES: CC1=C(C(C(=C(N1)C)C(=O)OC(C)C)C2=CC(=CC=C2)[N+](=O)[O-])C(=O)OCCOC
• Recent ClinicalTrials: Cognitive Effects of Nimodipine in Patients With Schizophrenia
• Recent EU Clinical Trials: Intraoperative application of nimodipine to the facial and cochlear nerves during vestibular schwannoma resection to avoid spasm-related postoperative facial paralysis and deafness - a prospective randomized study
• Indications: Nimodipine is a calcium antagonist of selective expansion of cerebral blood vessels. It can increase cerebral blood flow, improve cerebral blood circulation, prevent ischemic cerebral vasospasm, reduce calcium influx, protect ischemic brain cell function, prevent the occurrence and development of brain vascular disease and delay and prevent the occurrence of stroke. Nimodipine is mainly used for cerebral insufficiency, cerebral vasospasm, subarachnoid hemorrhage, stroke and migraine. It has a certain effect on sudden deafness.
• Uses: 1. Calcium channel blockers. Nimodipine has anti-ischemic and anti-vasoconstriction effect. It is the drug to improve cerebral vasodilator and brain function. It can be used for treating ischemic cerebrovascular disease, mild to moderate hypertension, migraine, cerebral vasospasm, sudden deafness and the like. 2. Calcium channel blockers. Nimodipine is mainly used for the treatment of ischemic cerebrovascular disease and migraine. 3. A new calcium antagonist. Nimodipine is used for the treatment of cerebrovascular disorders, such as cerebral vasospasm, interim and early ischemic cerebrovascular migraine, and sudden deafness. A dihydropyridine calcium channel blocker. It is used as a vasodilator (cerebral). provitamin, antixerophthalamic Nimodipine has been used:as a L-type calcium channel (LTCC) inhibitor, to evaluate its neuroprotective activity in the vibrosectionsas a standard, in the enantioseparation of chiral drugs by high performance liquid chromatography (HPLC)in the pharmacological studies for the measurement of spine voltage escape Used as a cerebral vasodilator. A dihydropyridine calcium channel blocker
• Production method: Method 1: Nimodipine can be synthesized from nitrobenzaldehyde first by condensation with methoxyethyl acetoacetate catalyzed by hydrochloric acid or concentrated sulfuric acid, and then heated with 3-amino butyric acid isopropyl ester in ethanol by cyclization. Method 2: Nitrobenzaldehyde and isopropyl acetoacetate also can be dissolved with stirring at room temperature firstly. Then add glacial acetic acid and piperidine and stir at 40-50℃ to solidify (about 6~7h). After processing for 4h at 40-50℃, 95% ethanol is added, and then heated under reflux until the solid dissolved. Cooled to 0~5℃, precipitated crystals can be filtered and dried to give 2-(3-nitrophenyl methylene) acetyl isopropyl acetate. The yield is 90.6%. Then it reacts with 3-amino butyric acid and 2-methoxy-ethyl ester to obtain the crude product. The crude product can be recrystallized from ethanol to get nimodipine. The yield is 84%, and the melting point is 125~126℃. The second step can also be carried out as follows: 3.8g 2-(3-nitrophenyl methylene) acetyl isopropyl acetate, 8g 2-methoxy-ethyl acetoacetate and 6ml of concentrated ammonia are heated at reflux for 8h in 80ml of ethanol. The product is recrystallized with petroleum ether-ethyl acetate to obtain nimodipine. The yield is 49%, and the melting point is 125℃.
• Description: Nimodipine is a cerebral vasodilating calcium antagonist related to nifedipine. It is indicated for the prophylaxis and treatment of neurological deficits due to cerebral vasospasm after subarachnoid hemorrhage.
• Therapeutic Function: Vasodilator
• Clinical Use: Calcium-channel blocker: Prevention and treatment of ischaemic neurological deficits following subarachnoid haemorrhage
• Drug interactions: Potentially hazardous interactions with other drugs Aminophylline: possibly increases aminophylline concentration. Anaesthetics: enhanced hypotensive effect. Antibacterials: metabolism accelerated by rifampicin; metabolism possibly inhibited by clarithromycin, erythromycin and telithromycin. Antidepressants: enhanced hypotensive effect with MAOIs . Antiepileptics: effect reduced by carbamazepine, barbiturates, phenytoin and primidone. Antifungals: metabolism possibly inhibited by itraconazole and ketoconazole; negative inotropic effect possibly increased with itraconazole. Antihypertensives: enhanced hypotensive effect, increased risk of first dose hypotensive effect of post synaptic alpha-blockers. Antivirals: concentration possibly increased by ritonavir; use telaprevir with caution. Grapefruit juice: concentration increased - avoid. Theophylline: possibly increased theophylline concentration.

Technology Process of Nimodipine

There total 10 articles about Nimodipine which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 81.0%

isopropyl 3-aminocrotonate (40100-28-5) + (E/Z)-2-methoxyethyl 2-(3-nitrobenzylidene)-acetoacetate (39562-22-6) → nimodipin (66085-59-4)

Guidance literature:

In ethanol; for 24h; Heating;

Reference yield: 69.0%

2-methoxyethyl-3-oxobutanoate (22502-03-0) + 3-nitro-benzaldehyde (99-61-6) + isopropyl β-aminocrotonate (143093-33-8) → nimodipin (66085-59-4) + 3,5-diisopropyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (21881-78-7)

Guidance literature:

In ethanol; for 16h; Heating;

DOI:10.1002/ardp.19973300109

Reference yield:

(+)-1,4-dihydro-2,6-dimethyl-4-(3'-nitrophenyl)-pyridine-3,5-dicarboxylic acid isopropyl-2(S)-methoxy-2-phenylethyl ester → nimodipin (66085-59-4)

Guidance literature:

With sodium; In 2-methoxy-ethanol; water;

upstream raw materials:

isopropyl 3-aminocrotonate

(E/Z)-2-methoxyethyl 2-(3-nitrobenzylidene)-acetoacetate

isopropyl acetoacetate

2-methoxyethyl-3-oxobutanoate

Downstream raw materials:

3,5-diisopropyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate

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

Refernces

• 1、 -. "Nimodipine impurity IV reference substance as well as preparation method and application thereof". . . Retrieved 2020/11/22.
• 2、 -. "Polymorph Compositions, Methods of Making, and Uses Thereof". . . Retrieved 2013/11/19.