Zuclopenthixol

Base Information

• Chemical Name: Zuclopenthixol
• CAS No.: 53772-83-1
• Molecular Formula: C₂₂H₂₅ClN₂OS
• Molecular Weight: 400.972
• European Community (EC) Number: 213-566-0,258-758-5,261-080-2
• UNII: 47ISU063SG
• DSSTox Substance ID: DTXSID3048233
• Nikkaji Number: J32.497C
• Wikipedia: Zuclopenthixol,Clopenthixol
• Wikidata: Q228143
• NCI Thesaurus Code: C154301,C66713,C95837
• Pharos Ligand ID: W34CD16VUPW2
• Metabolomics Workbench ID: 43608
• ChEMBL ID: CHEMBL53904
• Mol file: 53772-83-1.mol

Synonyms:alpha Clopenthixol;alpha-Clopenthixol;Cisordinol;Clopenthixol;Zuclopenthixol

Chemical Property of Zuclopenthixol

Chemical Property:

• Vapor Pressure: 3.56E-14mmHg at 25°C
• Melting Point: 56-60°C
• Refractive Index: 1.675
• Boiling Point: 577.4 °C at 760 mmHg
• PKA: 14.96±0.10(Predicted)
• Flash Point: 303 °C
• PSA: 52.01000
• Density: 1.289 g/cm³
• LogP: 4.11210
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility.: Chloroform (Slightly), Methanol (Slightly)
• XLogP3: 4.3
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 5
• Exact Mass: 400.1376123
• Heavy Atom Count: 27
• Complexity: 509

Purity/Quality:

99% ^*data from raw suppliers

Zuclopenthixol ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CN(CCN1CCC=C2C3=CC=CC=C3SC4=C2C=C(C=C4)Cl)CCO
• Isomeric SMILES: C1CN(CCN1CC/C=C\2/C3=CC=CC=C3SC4=C2C=C(C=C4)Cl)CCO
• Recent ClinicalTrials: Evaluation of the Necessity of Long-term Pharmacological Treatment With Antipsychotics in Schizophrenic Patients
• Recent EU Clinical Trials: PREemptive Pharmacogenomic testing for Preventing Adverse drug REactions
• Description: Zuclopenthixol is a dopamine receptor antagonist (Kis = 9.8 and 1.5 nM for D1 and D2 receptors, respectively). It also binds to serotonin (5-HT) receptor subtypes 5-HT2 and 5-HT6, α1-adrenergic, and histamine receptors (Kis = 7.6, 3, 33, and 169 nM, respectively) but not α2-adrenergic receptors (Ki = >4,300 nM). Zuclopenthixol inhibits dopamine-induced accumulation of cAMP in rat striatal homogenates (IC50 = 330 nM; Ki = 16 nM). It decreases stereotypic behavior induced by methylphenidate in mice (ED50 = 0.8 μmol/kg) and by apomorphine in rats and dogs (ED50s = 6.0 and 1.3 μmol/kg, respectively). Zuclopenthixol (0.7 and 1.4 mg/kg, i.p.) administered prior to testing enhances memory retrieval in rats in an inhibitory avoidance task without affecting locomotor activity. Zuclopenthixol is a kind of antipsychotic agent. It is a thioxanthene-based neuroleptic with in vivo action similar to the phenothiazine antipsychotics through antagonizing D1 and D2 dopamine receptors. It has three major formulations form including zuclopenthixol decanoate, zuclopenthixol acetate, and zuclopenthixol dihydrochloride. It can be used for the treatment of schizophrenia and bipolar mania. Besides antagonizing the D1 and D2 dopamine receptors, Zuclopenthixol can also take effect through antagonizing alpha1-adrenergic and 5-HT2 receptors. It can also weakly block the histamine H1 receptor.
• Uses: The cis(Z)-form of Clopenthixol. Thioxanthene neuroleptic. Antipsychotic. The labelled cis(Z)-form of Clopenthixol. Thioxanthene neuroleptic. Antipsychotic. Zuclopenthixol is an anti-psychotic drug. It is an inhibitor of coxsackievirus B3. Also, it is an intermediate used in the synthesis of Zuclopenthixol Decanoate (Z701490), which is used in the maintenance treatment of chronic schizophrenic patients. It is one of the three distinct formulations of Zuclopenthixol namely, zuclopenthixol dihydrochloride, zuclopenthixol acetate or Acuphase and zuclopenthixol decanoate.
• Clinical Use: Antipsychotic for schizophrenia and other psychoses
• Drug interactions: Potentially hazardous interactions with other drugs Anaesthetics: enhanced hypotensive effects. Analgesics: increased risk of convulsions with tramadol; enhanced hypotensive and sedative effects with opioids; increased risk of ventricular arrhythmias with methadone. Anti-arrhythmics: increased risk of ventricular arrhythmias with anti-arrhythmics that prolong the QT interval - avoid with amiodarone and disopyramide. Antibacterials: increased risk of ventricular arrhythmias with moxifloxacin and parenteral erythromycin - avoid Antidepressants: increased level of tricyclics; possible increased risk of convulsions with vortioxetine. Antiepileptics: anticonvulsant effect antagonised. Antimalarials: avoid concomitant use with artemether/lumefantrine. Antipsychotics: avoid concomitant use of clozapine with depot preparations in case of neutropenia; possible increased risk of ventricular arrhythmias with risperidone. Antivirals: concentration possibly increased with ritonavir. Atomoxetine: increased risk of ventricular arrhythmias. Anxiolytics and hypnotics: increased sedative effects. Beta-blockers: increased risk of ventricular arrhythmias with sotalol - avoid. Cytotoxics: increased risk of ventricular arrhythmias with vandetanib - avoid; increased risk of ventricular arrhythmias with arsenic trioxide.

Technology Process of Zuclopenthixol

There total 3 articles about Zuclopenthixol 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:

→ 4-[3-(2-chloro-9H-thioxanthen-9-ylidene)propyl]-1-piperazineethanol (982-24-1,53772-83-1,53772-84-2)

Guidance literature:

2-Chlor-9-<3-piperazino-propyliden>-thioxanthen, Aethylenoxid;

Reference yield:

tert-butyl 4-(benzoyloxy)piperazine-1-carboxylate (77278-40-1) + 2-Chlorothioxanthone (86-39-5) + 1,2-propanediene (463-49-0) + 2-bromoethanol (540-51-2) → clopenthixol (53772-83-1,53772-84-2) + zuclopenthixol (53772-83-1,53772-84-2)

Guidance literature:

2-Chlorothioxanthone; With copper diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In tetrahydrofuran; for 0.0833333h; Inert atmosphere;

1,2-propanediene; With (dimethoxy)methylsilane; In tetrahydrofuran; at 20 ℃; for 12h; Inert atmosphere; Schlenk technique;

tert-butyl 4-(benzoyloxy)piperazine-1-carboxylate; 2-bromoethanol; Overall yield = 54 %; Overall yield = 217 mg; Further stages;

DOI:10.1021/jacs.8b13907

Reference yield:

tert-butyl 4-(benzoyloxy)piperazine-1-carboxylate (77278-40-1) + 2-Chlorothioxanthone (86-39-5) + 1,2-propanediene (463-49-0) + 2-bromoethanol (540-51-2) → clopenthixol (53772-83-1,53772-84-2) + zuclopenthixol (53772-83-1,53772-84-2)

Guidance literature:

2-Chlorothioxanthone; With copper diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In tetrahydrofuran; for 0.0833333h; Inert atmosphere;

1,2-propanediene; With (dimethoxy)methylsilane; In tetrahydrofuran; at 20 ℃; for 12h; Inert atmosphere; Schlenk technique;

tert-butyl 4-(benzoyloxy)piperazine-1-carboxylate; 2-bromoethanol; Overall yield = 54 %; Overall yield = 217 mg; Further stages;

DOI:10.1021/jacs.8b13907

upstream raw materials:

tert-butyl 4-(benzoyloxy)piperazine-1-carboxylate

2-Chlorothioxanthone

1,2-propanediene

2-bromoethanol

Downstream raw materials:

zuclopenthixol acetate

Refernces