174794-02-6

Basic information

• Product Name: OLANZAPINE N-OXIDE
• Synonyms: Olanzapine Related Compound C (5 mg) (2-methyl-4-(4-methylpiperazin-1-yl)-10H-benzo[b]thieno[2,3-e][1,4]diazepine 4'-N-oxide);2-Methyl-4-(4-Methylpiperazin-1-yl)-10H-benzo[b]thieno[2,3-e][1,4]diazepine 4'-N-oxide;Olanzapine EP IMpurity D;Olanzapine N-oxide (Olanzapine IMpurity D);Olanzapine Related CoMpound C;Olanzapine Related Compound C (2-methyl-4-(4-methylpiperazin-1-yl)-10H-benzo[b]thieno[2,3-e][1,4]diazepine 4'-N-oxide);Olanzapine Related Impurity D;1-methyl-4-(2-methyl-10H-benzo[b]thieno[2,3-e][1,4]diazepin-4-yl)piperazine 1-oxide
• CAS NO: 174794-02-6
• Molecular Formula: C17H20N4OS
• Molecular Weight: 328.4319
• Product Categories: Heterocycles;Sulfur & Selenium Compounds;Various Metabolites and Impurities;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals
• Mol File: 174794-02-6.mol

Chemical Properties

• Melting Point: 214-216°C (dec.)
• Appearance: /
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 7.32±0.20(Predicted)
• CAS DataBase Reference: OLANZAPINE N-OXIDE(CAS DataBase Reference)
• NIST Chemistry Reference: OLANZAPINE N-OXIDE(174794-02-6)
• EPA Substance Registry System: OLANZAPINE N-OXIDE(174794-02-6)

Safety Data

• Safety Statements: 24/25
• Hazardous Substances Data: 174794-02-6(Hazardous Substances Data)

Usage

Chemical Properties

Yellow Solid

Uses

A metabolite of Olanzapine (Olanzapine EP Impurity D).

InChI:InChI=1/C17H20N4OS/c1-12-11-13-16(20-7-9-21(2,22)10-8-20)18-14-5-3-4-6-15(14)19-17(13)23-12/h3-6,11,19H,7-10H2,1-2H3

Upstream product

• 138564-60-0 4-amino-2-methyl-10H-thieno[2,3-b][1,5]benzodiazepine hydrochloride 
• 138564-58-6 2-amino-5-methylthiophene-3-carbonitrile 
• 138564-59-7 2-(2-nitroanilino)-5-methylthiophene-3-carbonitrile 
• 1493-27-2 ortho-nitrofluorobenzene 
• 109-01-3 1-methyl-piperazine 
• 132539-06-1 zyprexa 

Downstream Products

• 132539-06-1 zyprexa 
• 14371-10-9 (E)-3-phenylpropenal 

Relevant articles and documents

Individual differences in in vitro and in vivo metabolic clearances of the antipsychotic drug olanzapine from non-smoking and smoking Japanese subjects genotyped for cytochrome P4502D6 and flavincontaining monooxygenase 3

Objective The antipsychotic olanzapine is reportedly metabolized by inducible human cytochrome P450 (CYP) 1A2 and variable copy-number CYP2D6 and polymorphic flavin-containing monooxygenase 3 (FMO3) in different pathways. We investigated individual differences in the metabolite formation and clearance of olanzapine in vitro and in vivo. Methods Human liver microsomal olanzapine oxidation activities were evaluated, and plasma concentrations of olanzapine were determined in 21 Japanese patients (mean age: 50 years, range: 32-69 years, 14 male and 7 female, including 6 smokers) genotyped for CYP2D6 (1,5, and10) and FMO3 (E158K, C197fsX, R205C, V257M, E308G, and R500X). Results Furafylline (a CYP1A2 inhibitor), quinidine (a CYP2D6 inhibitor), and heat treatment (inactivates FMO3) suppressed liver microsomal metabolic clearance of olanzapine by approximately 30%. Olanzapine N-demethylation and N-oxygenation were found to be catalyzed by CYP1A2 and CYP2D6 and by CYP2D6 and FMO3, respectively, in experiments using liver microsomes and recombinant enzymes. Plasma concentrations and clearance of olanzapine were not affected by CYP2D6 or FMO3 genotypes or smoking behavior. Conclusions Olanzapine clearance was not affected by CYP2D6 or FMO3 genotypes or smoking behavior as a single factor under the present conditions because olanzapine clearance is mediated by multiple enzymes involved in two major and one minor pathways.

PROCESS FOR THE PREPARATION OF OLANZAPINE

The invention relates to a process for the preparation of 2 -methyl-4 - (4-methylpiperazin- 1-yl) - 10H- thieno- [2 , 3 -b] [1 , 5] benzodiazepine (olanzapine) of the formula (I) by reacting 4-amino-2-methyl-10H-thieno [2,3- b] [1/5] benzodiazepine hydrochloride of the formula (II) with N-methylpiperazine in an organic solvent, which comprises carrying out the reaction in the mixture of toluene and 1, 3-dimethyl-2- imidazolidinone . The invention also encompasses new 2-methyl-4- (4-methylpiperazin-l-yl) -10H-thieno [2,3- b] [1,5] benzodiazepine dihydrochloride trihydrate of the formula (IB) , the preparation thereof and pharmaceutical compositions comprising said new compound.

The synthesis and biological activity of some known and putative metabolites of the atypical antipsychotic agent olanzapine (LY170053)

4'-N-desmethyl olanzapine (2), olanzapine 4'-N-oxide (3) and 2-hydroxymethyl olanzapine (5), have been prepared and their pharmacology compared to that of the parent compound olanzapine (1). The 4'-N-quaternary glucuronide (8) has also been prepared.