2-[2-(4-{2-thia-9-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-10-yl}piperazin-1-yl)ethoxy]ethan-1-ol

• ChemBase ID: 1094
• Molecular Formular: C21H25N3O2S
• Molecular Mass: 383.5071
• Monoisotopic Mass: 383.16674806
• SMILES: S1c2c(C(=Nc3c1cccc3)N1CCN(CC1)CCOCCO)cccc2
• Canonical SMILES: OCCOCCN1CCN(CC1)C1=Nc2ccccc2Sc2c1cccc2
• InChI: InChI=1S/C21H25N3O2S/c25-14-16-26-15-13-23-9-11-24(12-10-23)21-17-5-1-3-7-19(17)27-20-8-4-2-6-18(20)22-21/h1-8,25H,9-16H2
• InChIKey: URKOMYMAXPYINW-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 2-[2-(4-{2-thia-9-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-10-yl}piperazin-1-yl)ethoxy]ethan-1-ol; 2-[2-(4-{2-thia-9-azatricyclo[9.4.0.0^3,^8]pentadeca-1(11),3(8),4,6,9,12,14-heptaen-10-yl}piperazin-1-yl)ethoxy]ethan-1-ol
• IUPAC Traditional name: quetiapine
• Brand Name: Seroquel; Seroquel XR
• Synonyms: Quetiapine fumarate; Quetiapine hemifumarate; Quetiapine; Seroquel; ICI-204636; 2-[2-(4-Dibenzo[b,f][1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]ethanol Bis[(2E)-2-Butenedioate]; Quetiapine Hemifumarate

Database IDs

• CAS Number: 111974-72-2; 111974-69-7
• PubChem SID: 160964557; 46504800
• PubChem CID: 5002

CALCULATED PROPERTIES

JChem

• Acid pKa: 15.121227
• H Acceptors: 5
• H Donor: 1
• LogD (pH = 5.5): 1.2358336
• LogD (pH = 7.4): 2.6430545
• Log P: 2.8079426
• Molar Refractivity: 114.0854 cm^3
• Polarizability: 42.748154 Å^3
• Polar Surface Area: 48.3 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.93
• LOG S: -3.98
• Solubility (Water): 4.03e-02 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; Methanol; Moderate
• Apperance: White Solid
• Melting Point: 174-176°C
• Hydrophobicity(logP): 2.8

Safety Information

• Storage Condition: -20°C Freezer

DETAILS

DrugBank - DB01224

• Drug Groups: approved
• Description: Quetiapine is indicated for the treatment of schizophrenia as well as for the treatment of acute manic episodes associated with bipolar I disorder. The antipsychotic effect of quetiapine is thought by some to be mediated through antagonist activity at dopamine and serotonin receptors. Specifically the D1 and D2 dopamine, the alpha 1 adrenoreceptor and alpha 2 adrenoreceptor, and 5-HT1A and 5-HT2 serotonin receptor subtypes are antagonized. Quetiapine also has an antagonistic effect on the histamine H1 receptor.
• Indication: For the treatment of schizophrenia and related psychotic disorders.
• Pharmacology: Quetiapine is a psychotropic agent belonging to the chemical class of benzisoxazole derivatives and is indicated for the treatment of schizophrenia. Quetiapine is a selective monoaminergic antagonist with high affinity for the serotonin Type 2 (5HT₂), and dopamine type 2 (D2) receptors. Quetiapine is an antagonist at serotonin 5-HT_1A and 5HT₂, dopamine D1 and D2, histamine H1, and adrenergic alpha 1 and alpha 2 receptors. Quetiapine has no significant affinity for cholinergic muscarinic or benzodiazepine receptors. Drowsiness and orthostatic hypotension associated with use of quetiapine may be explained by its antagonism of histamine H1 and adrenergic alpha 1 receptors, respectively. Quetiapine's antagonism of adrenergic a1 receptors may explain the orthostatic hypotension observed with this drug.
• Toxicity: Symptoms of overdose include drowsiness and sedation, tachycardia, and hypotension.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. The major metabolic pathways are sulfoxidation, mediated by cytochrome P450 3A4 (CYP3A4), and oxidation of the terminal alcohol to a carboxylic acid. The major sulfoxide metabolite of quetiapine is inactive. Quetiapine also undergoes hydroxylation of the dibenzothiazepine ring, O-deakylation, N-dealkylation, and phase II conjugation. The 7-hydroxy and 7-hydroxy-; N-delakylated metabolites appear to be active, but are present in very low concentrations.
• Absorption: Rapidly and well absorbed.
• Half Life: 6 hours
• Protein Binding: 83%
• Elimination: Elimination of quetiapine is mainly via hepatic metabolism. Following a single oral dose of 14C-quetiapine, less than 1% of the administered dose was excreted as unchanged drug, indicating that quetiapine is highly metabolized. Approximately 73% and 20% of the dose was recovered in the urine and feces, respectively.
• Distribution: * 10±4 L/kg
• References: Dev V, Raniwalla J: Quetiapine: a review of its safety in the management of schizophrenia. Drug Saf. 2000 Oct;23(4):295-307. [Pubmed] ; Mukaddes NM, Abali O: Quetiapine treatment of children and adolescents with Tourette's disorder. J Child Adolesc Psychopharmacol. 2003 Fall;13(3):295-9. [Pubmed] ; Tallerico T, Novak G, Liu IS, Ulpian C, Seeman P: Schizophrenia: elevated mRNA for dopamine D2(Longer) receptors in frontal cortex. Brain Res Mol Brain Res. 2001 Mar 5;87(2):160-5. [Pubmed] ; Urichuk L, Prior TI, Dursun S, Baker G: Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions. Curr Drug Metab. 2008 Jun;9(5):410-8. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Toronto Research Chemicals - Q510000

Used as an antipsychotic. Benzothiazepine with mixed serotonin and dopamine receptor antagonistic properties.

REFERENCES

• Dev V, Raniwalla J: Quetiapine: a review of its safety in the management of schizophrenia. Drug Saf. 2000 Oct;23(4):295-307. Pubmed
• Mukaddes NM, Abali O: Quetiapine treatment of children and adolescents with Tourette's disorder. J Child Adolesc Psychopharmacol. 2003 Fall;13(3):295-9. Pubmed
• Tallerico T, Novak G, Liu IS, Ulpian C, Seeman P: Schizophrenia: elevated mRNA for dopamine D2(Longer) receptors in frontal cortex. Brain Res Mol Brain Res. 2001 Mar 5;87(2):160-5. Pubmed
• Urichuk L, Prior TI, Dursun S, Baker G: Metabolism of atypical antipsychotics: involvement of cytochrome p450 enzymes and relevance for drug-drug interactions. Curr Drug Metab. 2008 Jun;9(5):410-8. Pubmed
• Wetzel, H., et al.: Psychopharmacology, 119, 231 (1995)