Aripiprazole

Base Information

• Chemical Name: Aripiprazole
• CAS No.: 129722-12-9
• Molecular Formula: C23H27Cl2N3O2
• Molecular Weight: 448.392
• Hs Code.: 29349990
• European Community (EC) Number: 603-355-5,685-520-1
• NSC Number: 759266
• UNII: 82VFR53I78
• DSSTox Substance ID: DTXSID3046083
• Nikkaji Number: J573.417G
• Wikipedia: Aripiprazole
• Wikidata: Q411188
• NCI Thesaurus Code: C47403
• RXCUI: 89013
• Pharos Ligand ID: NY2L457GCS5B
• Metabolomics Workbench ID: 38723
• ChEMBL ID: CHEMBL1112
• Mol file: 129722-12-9.mol

Synonyms:7-(4-(4-(2,3-dichlorophenyl)-1-piperazinyl)butyloxy)-3,4-dihydro-2(1H)-quinolinone;Abilify;Aripiprazol;aripiprazole;OPC 14597;OPC-14597

Chemical Property of Aripiprazole

Chemical Property:

• Appearance/Colour: colourless flake crystalline solid
• Vapor Pressure: 1.38E-16mmHg at 25°C
• Melting Point: 139 °C
• Refractive Index: 1.593
• Boiling Point: 646.2 °C at 760 mmHg
• PKA: 14.42±0.20(Predicted)
• Flash Point: 344.6 °C
• PSA: 44.81000
• Density: 1.263 g/cm³
• LogP: 5.00020
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO: soluble5mg/mL, clear (warmed)
• XLogP3: 4.6
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 7
• Exact Mass: 447.1480325
• Heavy Atom Count: 30
• Complexity: 559

Purity/Quality:

98% up, ^*data from raw suppliers

Aripiprazole ^*data from reagent suppliers

Safty Information:

• Pictogram(s): F,Xn
• Hazard Codes: F,Xn
• Statements: 11-20/21/22-36
• Safety Statements: 16-36/37

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antipsychotic Agents
• Canonical SMILES: C1CC(=O)NC2=C1C=CC(=C2)OCCCCN3CCN(CC3)C4=C(C(=CC=C4)Cl)Cl
• Recent ClinicalTrials: Aripiprazole in Body Focused Repetitive Behaviors
• Recent EU Clinical Trials: Open, multicenter, randomized clinical trial to evaluate the efficacy and safety of aripiprazole vs paliperidone / risperidone using multi-omics data in patients with a first psychotic episode.
• Recent NIPH Clinical Trials: The study about anti-depression mechanism of dopamine partial agonist
• Drug Interactions: 1.It should be used with caution in combination with drugs acting on the central nervous system and alcohol. 2. aripiprazole has possibility of enhancing the role of certain antihypertensive drugs. 3. CYP3A4 inducer will result in elevated aripiprazole clearance and lower blood concentration, CYP3A4 inhibitor azole) or CYP2D inhibitors can inhibit aripiprazole elimination, increase plasma concentration.
• Uses: Antipsychotics A deuterated version of Aripiprazole, a selective dopamine D2-receptor antagonist with dopamine autoreceptor agonist activity. Please note that users have reported separation of this compound and aripiprazole under normal-phase and reverse-phase A selective dopamine D2-receptor antagonist with dopamine autoreceptor agonist activity. Antipsychotic. cerebral vasodilator, antimotion For the treatment of schizophrenia and related psychotic disorders.
• Description: Aripiprazole was launched for the treatment of psychoses including schizophrenia and offers a novel mechanism of action as a partial D2 receptor agonist. Aripiprazole can be synthesized in three steps beginning by the condensation of 7-hydroxy-1,2,3,4- tetrahydroquinolin-2-one with 1 ,Cdibromobutane followed by reaction with 1-(2,3- dichlorophenyl)piperazine. Aripiprazole is a significant D2 agonist/antagonist, 5-HT2 antagonist and 5-HT1α agonist combined with minimal affinity for a,-adrenergic, H1 and M1 receptors. It has a low D4:D2 selectivity ratio and a D2:5-HT2 affinity ratio that exceeds 15; resulting in different pharmacological characteristics compared to other atypical antipsychotics agents such as clozapine. In animal models, aripiprazole inhibits apomorphine-induced stereotypy without causing catalepsy and ptosis. Moreover, in contrast to classical antipsychotics that produce disabling movement disorders, aripiprazole does not cause an upregulation of D2 receptors or an increase in immediate early gene expression of e.g. the c-fos mRNA in the striatum. In patients with acute relapse of schizophrenia, treatment with aripiprazole provided significant improvement in both positive and negative syndrome scale (PANSS) total score in both short- and longterm evaluations. These results were comparable to those observed with haloperidol or risperidone; however, the early response rate was greater with aripiprazole. Aripiprazole was well tolerated with mild to moderate adverse events such as nausea, dizziness, somnolence and weight gain. The rates of extrapyramidal symptoms were lower than with haloperidol, prolactin levels increase has been uncommon and no significant Q-Tc interval prolongation was observed compared with placebo. Finally, studies suggested a minimal impact of aripiprazole administration on total cholesterol levels and on fasting blood sugar in contrast to other antipsychotics. Aripiprazole has a bioavailability of 87%, a tmax of 3-5 h and a half-life time of 48-68 h. Aripiprazole has been found to have linear kinetics and is mainly metabolized via the cytochrome systems CYP2D6 and CYP3A4. It has little effect on the blood levels of other medications; interaction with both lithium and divalproex sodium found minimal impact. Aripiprazole has also been studied in other psychiatric disorders, including bipolar disorders and has shown great efficacy.
• Therapeutic Function: Antipsychotic
• Clinical Use: Atypical antipsychotic: Treatment of schizophrenia Depression in bipolar disorder
• Drug interactions: Potentially hazardous interactions with other drugs Anaesthetics: enhanced hypotensive effect. Analgesics: increased risk of convulsions with tramadol; enhanced hypotensive and sedative effects with opioids; increased risk of ventricular arrhythmias with methadone. Antihypertensives: may enhance antihypertensive effect. Alcohol and other CNS drugs: increased sedation and other related side effects. Anti-arrhythmics: increased risk of ventricular arrhythmias with anti-arrhythmics that prolong the QT interval. Antibacterials: concentration possibly reduced by rifabutin and rifampicin - increase dose of aripiprazole. Antidepressants: fluoxetine and paroxetine possibly inhibit metabolism - reduce dose of aripiprazole; concentration possibly reduced by St John’s wort - increase aripiprazole dose; increased concentration of tricyclics. Antiepileptics: antagonises anticonvulsant effect; concentration reduced by carbamazepine and possibly reduced by fosphenytoin, phenytoin, phenobarbital and primidone - increase dose of aripiprazole. Antifungals: metabolism inhibited by ketoconazole and possibly by itraconazole - reduce dose of aripiprazole. Antimalarials: avoid with artemether/lumefantrine. Antipsychotics: possible increased risk of ventricular arrhythmias with risperidone. Antivirals: metabolism possibly inhibited by atazanavir, darunavir, fosamprenavir, indinavir, lopinavir, ritonavir, saquinavir and tipranavir - reduce dose of aripiprazole; concentration possibly reduced by efavirenz and nevirapine - increase dose of aripiprazole. Anxiolytics and hypnotics: increased sedative effects. Atomoxetine: increased risk of ventricular arrhythmias. Cytotoxics: increased risk of ventricular arrhythmias with arsenic trioxide.

Technology Process of Aripiprazole

There total 54 articles about Aripiprazole 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: 99.3%

Aripiprazole hydrochloride (1026778-41-5) → aripiprazole (129722-12-9)

Guidance literature:

at 100 - 120 ℃; for 21h; Industrial scale;

Reference yield: 98.0%

1-(2,3-dichlorophenyl)-piperazine hydrochloride (119532-26-2,864512-47-0) + 7-(4-chlorobutoxy)-3,4-dihydroquinoline-2(1H)-one (120004-79-7) → aripiprazole (129722-12-9)

Guidance literature:

With potassium carbonate; In water; for 3h; Reflux;

Reference yield: 94.0%

carbon monoxide (201230-82-2) + 1-(2,3-dichlorophenyl)-4-(4-(3-nitro-4-vinylphenoxy)butyl)piperazine → aripiprazole (129722-12-9)

Guidance literature:

With palladium (II) nitrate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In tetrahydrofuran; water; at 50 ℃; for 20h; under 30003 Torr; Pressure; Temperature; Reagent/catalyst;

upstream raw materials:

1-(2,3-dichlorophenyl)piperazine

7-(4-bromobutoxy)-3,4-dihydro-2(1H)-quinolinone

toluene-4-sulfonic acid

7-(allyloxy)-3,4-dihydro-2(1H)-quinolinone

Downstream raw materials:

OPC 14857

Aripiprazole hydrochloride

aripiprazole monohydrate

7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3,4-dihydro-2(1H)-quinolinone methanol solvate

Refernces

• 1、 Chen, Kaixuan,Jiang, Zhenzhou,Liu, Shuwen,Xi, Baomin,Yang, Fubiao,Zeng, Li-Yan,Zeng, Yunong. "The one-pot synthesis of butyl-1H-indol-3-alkylcarboxylic acid derivatives in ionic liquid as potent dual-acting agent for management of BPH". . . Retrieved 2020/09/18.
• 2、 -. "Preparation method of aripiprazole". Paragraph 0068-0074. . Retrieved 2019/10/01.