Quinidine

Base Information

• Chemical Name: Quinidine
• CAS No.: 56-54-2
• Deprecated CAS: 11010-73-4,500225-45-6,845886-64-8,882741-47-1,883881-01-4,898814-00-1,910899-51-3,1528764-92-2,2393956-08-4,1528764-92-2,500225-45-6,845886-64-8,882741-47-1,883881-01-4,910899-51-3
• Molecular Formula: C20H24N2O2
• Molecular Weight: 324.423
• Hs Code.: 29392000
• European Community (EC) Number: 200-279-0
• UN Number: 2811
• UNII: ITX08688JL
• DSSTox Substance ID: DTXSID4023549
• Wikipedia: Quinidine
• Wikidata: Q412496
• NCI Thesaurus Code: C793
• RXCUI: 9068
• Pharos Ligand ID: TTP6PN9UM1K1
• Metabolomics Workbench ID: 43177
• ChEMBL ID: CHEMBL1294
• Mol file: 56-54-2.mol

Synonyms:Adaquin;Apo Quinidine;Apo-Quinidine;Chinidin;Quincardine;Quinidex;Quinidine;Quinidine Sulfate;Quinora;Sulfate, Quinidine

Chemical Property of Quinidine

Chemical Property:

• Appearance/Colour: white to light yellow crystal powder
• Vapor Pressure: 0mmHg at 25°C
• Melting Point: 168-172 °C(lit.)
• Refractive Index: 1.5700 (estimate)
• Boiling Point: 495.9 °C at 760 mmHg
• PKA: 5.4, 10.0(at 20℃)
• Flash Point: 253.7 °C
• PSA: 45.59000
• Density: 1.218 g/cm³
• LogP: 3.11110
• Storage Temp.: Store at -20°C
• Sensitive.: Light Sensitive
• Solubility.: insoluble in H2O; ≥10.32 mg/mL in EtOH with ultrasonic; ≥11.95 mg/mL in DMSO
• Water Solubility.: 0.05 g/100 mL (20 ºC)
• XLogP3: 2.9
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 4
• Exact Mass: 324.183778013
• Heavy Atom Count: 24
• Complexity: 457
• Transport DOT Label: Poison

Purity/Quality:

99.5% ^*data from raw suppliers

Quinidine ^*data from reagent suppliers

Safty Information:

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

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Chemical Classes: Biological Agents -> Plant Toxins
• Drug Classes: Antiarrhythmic Agents
• Canonical SMILES: COC1=CC2=C(C=CN=C2C=C1)C(C3CC4CCN3CC4C=C)O
• Isomeric SMILES: COC1=CC2=C(C=CN=C2C=C1)[C@@H]([C@H]3C[C@@H]4CCN3C[C@@H]4C=C)O
• Recent ClinicalTrials: Drug-Drug Interaction Study Between EDP-235, Itraconazole, Carbamazepine and Quinidine in Healthy Subjects.
• Recent EU Clinical Trials: Quinidine versus verapamil in short-coupled idiopathic ventricular fibrillation: An open label, randomized crossover pilot trial
• Recent NIPH Clinical Trials: Quinidine sulfate administration for intractable epilepsy with KCNT1 gene mutation
• Description: Quinidine is a commonly used class I antiarrhythmic drug. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree. It exerts its antiarrhythmic effects on the heart by interacting with the electrophysiology mechanisms that cause arrhythmias to modify the abnormalities in impulse initiation and conduction. Quinidine depresses normal automaticity in cardiac fibers that may act as ectopic pacemakers causing arrhythmias. Quinidine also blocks the slowly inactivating, tetrodotoxin-sensitive Na current, the slow inward calcium current (ICa), the rapid (IKr) and slow (IKs) components of the delayed potassium rectifier current, the inward potassium rectifier current (IKI), the ATP-sensitive potassium channel (IKATP) and Ito. Quinidine is a stereoisomer of the antimalarial agent quinine and a class Ia antiarrhythmic agent. Quinidine blocks the voltage-gated sodium (Nav) channel Nav1.5 in a use-dependent manner. It decreases the amplitude and duration of action potentials in isolated canine ventricular myocytes. It inhibits KKr, peak INa, and late INa (IC50s = 4.5, 11, and 12 μM, respectively) and can induce torsade de pointes in isolated rabbit hearts when used at a concentration of 1 μM. Quinidine induces QT prolongation in dogs. It also binds to M2 muscarinic acetylcholine receptors (Ki = 7.5 μM for human recombinant receptors expressed in HM2-B10 cells). Formulations containing quinidine have been used in the treatment of atrial fibrillation and ventricular arrhythmias.
• Physical properties: Appearance: Quinidine is commonly used in its sulfate form with white needle-like crystal and bitter smell. It changes color easily when exposed to light. Solubility: It was soluble in ethanol and chloroform. Its water solubility is 0.05?g/100?mL (20?°C). Specific optical rotation: 256° (c?=?1, EtOH). Melting point: 168–172?°C.
• Uses: A dextrorotatory stereoisomer of Quinine. Antiarrhythmic (class IA). Antimalarial Quinidine occurs in cinchona bark to about0.25–0.3% and also in cuprea bark. It is present in quinine sulfate mother liquor. Itis formed by isomerization of quinine. Itis used in the prevention of certain cardiacarrhythmias.
• Indications: Quinidine acts as a class I antiarrhythmic agent (Ia) in the heart. It was clinically applicable to the treatment of recurrent, documented, life-threatening ventricular arrhythmias .
• Biological Functions: Quinidine is an alkaloid obtained from various species of Cinchona or its hybrids, from Remijia pedunculata, or from quinine. Quinidine is the dextrorotatory isomer of quinine.Quinidine (Quinidex) was one of the first clinically used antiarrhythmic agents. Because of the high incidence of ventricular proarrhythmia associated with its use and numerous other equally efficacious agents, quinidine is now used sparingly. Quinidine shares all of the pharmacological properties of quinine, including antimalarial, antipyretic, oxytocic, and skeletal muscle relaxant actions.
• Clinical Use: Primary indications for the use of quinidine include (1) abolition of premature complexes that have an atrial, A-V junctional, or ventricular origin; (2) restoration of normal sinus rhythm in atrial flutter and atrial fibrillation after controlling the ventricular rate with digitalis; (3) maintenance of normal sinus rhythm after electrical conversion of atrial arrhythmias; (4) prophylaxis against arrhythmias associated with electrical countershock; (5) termination of ventricular tachycardia; and (6) suppression of repetitive tachycardia associated with Wolff- Parkinson-White (WPW) syndrome. Although quinidine often is successful in producing normal sinus rhythm, its administration in the presence of a rapid atrial rate (flutter and possibly atrial fibrillation) can lead to a further and dangerous increase in the ventricular rate secondary to inhibition of basal vagal tone upon the A-V node. For this reason, digitalis should be used before quinidine when one is attempting to convert atrial flutter or atrial fibrillation to normal sinus rhythm.
• Drug interactions: Quinidine can increase the plasma concentrations of digoxin, which may in turn lead to signs and symptoms of digitalis toxicity. Gastrointestinal, central nervous system (CNS), or cardiac toxicity associated with elevated digoxin concentrations may occur.Quinidine and digoxin can be administered concurrently; however, a downward adjustment in the digoxin dose may be required. Drugs that have been associated with elevations in quinidine concentrations include acetazolamide, the antacids magnesium hydroxide and calcium carbonate, and the H2-receptor antagonist cimetidine. Cimetidine inhibits the hepatic metabolism of quinidine. Phenytoin, rifampin, and barbiturates increase the hepatic metabolism of quinidine and reduce its plasma concentrations.

Technology Process of Quinidine

There total 120 articles about Quinidine 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: 95.0%

quinidine acetate (56652-53-0) → quinindine (56-54-2,130-95-0,572-59-8,572-60-1,42151-59-7,47342-58-5,72402-50-7,72402-51-8,72402-52-9,72402-53-0,101143-86-6,101143-87-7,101143-88-8,146925-10-2)

Guidance literature:

With methanol; potassium carbonate; at 20 ℃; for 1.5h; Inert atmosphere;

DOI:10.1016/j.tetlet.2010.12.066

Reference yield: 75.0%

(3R,4S)-4-[(2S,3S)-3-(6-Methoxy-quinolin-4-yl)-oxiranylmethyl]-3-vinyl-piperidine-1-carboxylic acid 2-trimethylsilanyl-ethyl ester (865853-19-6) → quinindine (56-54-2,130-95-0,572-59-8,572-60-1,42151-59-7,47342-58-5,72402-50-7,72402-51-8,72402-52-9,72402-53-0,101143-86-6,101143-87-7,101143-88-8,146925-10-2)

Guidance literature:

With cesium fluoride;

DOI:10.1016/j.tetlet.2005.06.171

Reference yield:

6-Methoxy-4-[(2S,3S)-3-((3R,4S)-3-vinyl-piperidin-4-ylmethyl)-oxiranyl]-quinoline → quinindine (56-54-2,130-95-0,572-59-8,572-60-1,42151-59-7,47342-58-5,72402-50-7,72402-51-8,72402-52-9,72402-53-0,101143-86-6,101143-87-7,101143-88-8,146925-10-2)

Guidance literature:

In acetonitrile; at 185 ℃; for 0.333333h; Microwave irradiation;

DOI:10.1021/ja039550y

upstream raw materials:

Quinine

sodium ethanolate

6'-methoxy-cinchonan-9-one

pentan-1-ol

Downstream raw materials:

N-benzylquinidinium chloride

viquidil

O-tosylquinidine

6-methoxyquinoline-4-carboxylic acid

Refernces

• 1、 Jiang, Yan,Deiana, Luca,Zhang, Kaiheng,Lin, Shuangzheng,Córdova, Armando. "Total Asymmetric Synthesis of Quinine, Quinidine, and Analogues via Catalytic Enantioselective Cascade Transformations". supporting information. p. 6016 - 6023. Retrieved 2019/08/26.
• 2、 Sekikawa, Tohru,Kitaguchi, Takayuki,Kitaura, Hayato,Minami, Tatsuya,Hatanaka, Yasuo. "Anti-Selective Asymmetric Nitro-Michael Reaction of Furanones: Diastereocontrol by Catalyst". supporting information. p. 646 - 649. Retrieved 2016/03/01.