Nicardipine hydrochloride

Base Information

• Chemical Name: Nicardipine hydrochloride
• CAS No.: 54527-84-3
• Molecular Formula: C₂₆H₂₉N₃O₆*ClH
• Molecular Weight: 515.994
• Hs Code.: 2933399090
• European Community (EC) Number: 259-198-4,274-007-4
• NSC Number: 757855
• UNII: K5BC5011K3
• DSSTox Substance ID: DTXSID9046992
• Wikidata: Q27281986
• NCI Thesaurus Code: C29840
• RXCUI: 235230
• ChEMBL ID: CHEMBL1200326,CHEMBL3199626
• Mol file: 54527-84-3.mol

Synonyms:Antagonil;Cardene;Cardene I.V.;Cardene SR;Dagan;Flusemide;Hydrochloride, Nicardipine;LA, Nicardipine;Lecibral;Lincil;Loxen;Lucenfal;Nicardipine;Nicardipine Hydrochloride;Nicardipine LA;Nicardipino Ratiopharm;Nicardipino Seid;Perdipine;Ridene;Vasonase;Y 93;Y-93;Y93

Chemical Property of Nicardipine hydrochloride

Chemical Property:

• Appearance/Colour: Yellow solid
• Vapor Pressure: 1.63E-14mmHg at 25°C
• Melting Point: 176-178 °C
• Boiling Point: 603.4 °C at 760 mmHg
• Flash Point: 318.7 °C
• PSA: 113.69000
• LogP: 5.33180
• Storage Temp.: 2-8°C
• Solubility.: DMSO: ~1 mg/mL
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 8
• Rotatable Bond Count: 10
• Exact Mass: 515.1823134
• Heavy Atom Count: 36
• Complexity: 856

Purity/Quality:

99% ^*data from raw suppliers

Nicardipine Hydrochloride ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T
• Statements: 23/24/25
• Safety Statements: 36/37/39-45

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=C(C(C(=C(N1)C)C(=O)OCCN(C)CC2=CC=CC=C2)C3=CC(=CC=C3)[N+](=O)[O-])C(=O)OC.Cl
• Recent ClinicalTrials: A Study of the Pharmacokinetic and Pharmacodynamic Responses in Healthy and Altered Human Cardiovascular Systems
• Recent EU Clinical Trials: Comparison of efficacy between dexmedetomidine (DEX) and nicardipine (NIC) in adult facial surgery
• Description: Nicardipine is a dihydropyridine L-type calcium channel antagonist that displays antihypertensive and antianginal activity. It is reported to inhibit adenosine A1, A2A, and A3 receptors with Ki values of 19.6, 63.8, and 3.25 μM, respectively, and can inhibit cytochrome P450 3A4 catalytic activity with an IC50 value of 0.148 μM. Additionally, nicardipine has been shown to activate transient receptor potential A1 channels, producing an increase in Ca2+ (EC50 = 0.5 μM).
• Uses: anesthetic (topical) Nicardipine is a dihydropyridine L-type calcium channel antagonist that displays antihypertensive and antianginal activity. It is reported to inhibit adenosine A1, A2A, and A3 receptors with Ki values of 19.6, 63.8, and 3.25 μM, respectively, and can inhibit cytochrome P450 3A4 catalytic activity with an IC50 value of 0.148 μM. Additionally, nicardipine has been shown to activate transient receptor potential A1 channels, producing an increase in Ca2+ (EC50 = 0.5 μM).
• Clinical Use: Calcium-channel blocker: Prophylaxis and treatment of angina Mild to moderate hypertension Acute life-threatening hypertension and post operative hypertension (IV)
• Drug interactions: Potentially hazardous interactions with other drugs Aminophylline: possibly increases aminophylline concentration. Anaesthetics: enhanced hypotensive effect. Antibacterials: metabolism possibly 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. Cardiac glycosides: digoxin concentration increased. Ciclosporin: concentration of ciclosporin increased Grapefruit juice: concentration increased - avoid. Tacrolimus: may increase tacrolimus levels. Theophylline: possibly increased theophylline concentration.

Technology Process of Nicardipine hydrochloride

There total 8 articles about Nicardipine hydrochloride 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: 66.0%

methanesulfonyloxyethyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (103785-47-3) + benzyl-methyl-amine (103-67-3) → nicardipine hydrochloride (54527-84-3,69441-18-5,118705-95-6,118934-78-4)

Guidance literature:

With hydrogenchloride; at 95 ℃; for 8h;

DOI:10.1248/cpb.34.1589

Reference yield: 30.4%

acetoacetic acid [2-(N-methyl-N-benzylamino)-ethyl]-ester (54527-65-0) + 3-nitro-benzaldehyde (99-61-6) + methyl (E)-3-aminocrotonate (14205-39-1) → nicardipine hydrochloride (54527-84-3,69441-18-5,118705-95-6,118934-78-4)

Guidance literature:

acetoacetic acid [2-(N-methyl-N-benzylamino)-ethyl]-ester; 3-nitro-benzaldehyde; methyl (E)-3-aminocrotonate; In isopropyl alcohol; at 80 ℃;

With hydrogenchloride; In water; ethyl acetate; Product distribution / selectivity;

Reference yield:

methyl 2-(3-nitrophenylmethylene)acetoacetate (39562-17-9) + 2-(N-benzyl-N-methylamino)-ethyl 3-aminocrotonate (54527-73-0) → nicardipine hydrochloride (54527-84-3,69441-18-5,118705-95-6,118934-78-4)

Guidance literature:

In methanol; chloroform; ethyl acetate; acetone;

upstream raw materials:

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

benzyl-methyl-amine

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

acetoacetic acid [2-(N-methyl-N-benzylamino)-ethyl]-ester

Downstream raw materials:

2-(N-benzyl-N-methyl)amino-1-ethanol

C₁₆H₁₅N₂O₆^(1-)*Na⁽¹⁺⁾

2,6-Dimethyl-4-(3-nitro-phenyl)-pyridine-3,5-dicarboxylic acid 3-[2-(benzyl-methyl-amino)-ethyl] ester 5-methyl ester; hydrochloride

Refernces

• 1、 Zhang, Ping,Weeranoppanant, Nopphon,Thomas, Dale A.,Tahara, Kohei,Stelzer, Torsten,Russell, Mary Grace,O'Mahony, Marcus,Myerson, Allan S.,Lin, Hongkun,Kelly, Liam P.,Jensen, Klavs F.,Jamison, Timothy F.,Dai, Chunhui,Cui, Yuqing,Briggs, Naomi,Beingessner, Rachel L.,Adamo, Andrea. "Advanced Continuous Flow Platform for On-Demand Pharmaceutical Manufacturing". . p. 2776 - 2784. Retrieved 2018/02/06.
• 2、 -. "Novel process for producing 2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate-3-methyl ester-5-beta-(N-benzyl-N-methylamino)ethyl ester". . . Retrieved 2008/06/13.