4444-42-2

Basic information

• Product Name: desmethylnortriptyline
• Synonyms: desmethylnortriptyline;3-(10,11-Dihydro-5H-dibenzo[a,d]cycloheptene-5-ylidene)-1-propaneamine;3-[(10,11-Dihydro-5H-dibenzo[a,d]cyclohepten)-5-ylidene]-1-propanamine;Dinortriptyline;3-(10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-ylidene)propan-1-amine(WXG02098)
• CAS NO: 4444-42-2
• Molecular Formula: C₁₈H₁₉N
• Molecular Weight: 249.35
• Mol File: 4444-42-2.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 399.2°C at 760 mmHg
• Flash Point: 191.8°C
• Appearance: /
• Density: 1.127g/cm³
• Vapor Pressure: 1.39E-06mmHg at 25°C
• Refractive Index: 1.664
• Storage Temp.: -20°C Freezer
• Solubility: Chloroform (Slightly), Methanol (Slightly)
• CAS DataBase Reference: desmethylnortriptyline(CAS DataBase Reference)
• NIST Chemistry Reference: desmethylnortriptyline(4444-42-2)
• EPA Substance Registry System: desmethylnortriptyline(4444-42-2)

Safety Data

• Hazardous Substances Data: 4444-42-2(Hazardous Substances Data)

Usage

Uses

Desmethylnortriptyline is a metabolite of Nortriptyline which is used in the treatment of depression and migraines.

InChI:InChI=1/C18H19N/c19-13-5-10-18-16-8-3-1-6-14(16)11-12-15-7-2-4-9-17(15)18/h1-4,6-10H,5,11-13,19H2

Upstream product

• 549-18-8 amitriptyline hydrochloride 
• 50-48-6 amitryptyline 
• 72-69-5 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N-methyl-1-propanamine 

Downstream Products

• 50-48-6 amitryptyline 
• 72-69-5 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)-N-methyl-1-propanamine 

Relevant articles and documents

Drug Oxidation by Cytochrome P450BM3: Metabolite Synthesis and Discovering New P450 Reaction Types

There is intense interest in late-stage catalytic C-H bond functionalization as an integral part of synthesis. Effective catalysts must have a broad substrate range and tolerate diverse functional groups. Drug molecules provide a good test of these attributes of a catalyst. A library of P450BM3 mutants developed from four base mutants with high activity for hydrocarbon oxidation produced human metabolites of a panel of drugs that included neutral (chlorzoxazone, testosterone), cationic (amitriptyline, lidocaine) and anionic (diclofenac, naproxen) compounds. No single mutant was active for all the tested drugs but multiple variants in the library showed high activity with each compound. The high conversions enabled full product characterization that led to the discovery of the new P450 reaction type of oxidative decarboxylation of an α-hydroxy carboxylic acid and the formation a protected imine from an amine, offering a novel route to α-functionalization of amines. The substrate range and varied product profiles suggest that this library of enzymes is a good basis for developing late-stage C-H activation catalysts.

Regioselectivity and substrate concentration-dependency of involvement of the CYP2D subfamily in oxidative metabolism of amitriptyline and nortriptyline in rat liver microsomes

Kinetic analysis of the metabolism of amitriptyline and nortriptyline using liver microsomes from Wistar rats showed that more than one enzyme was involved in each reaction except for monophasic amitriptyline N-demethylation. The V(max) values particularly in the high-affinity sites for E-10-hydroxylation of both drugs were larger than those for Z-10-hydroxylations. Their E- and Z-10-hydroxylase activities in Dark-Agouti rats, which are deficient for CYP2D1, were significantly lower than those in Wistar rats at a lower substrate concentration (5 μM). The strain difference was reduced at a higher substrate concentration (500 μM). A similar but a smaller strain difference was also observed in nortriptyline N-demethylase activity, and a pronounced sex difference (male > female) was observed in N-demethylation of both drugs in Wistar and Dark-Agouti rats. The reactions with the strain difference were inhibited concentration-dependently by sparteine, a substrate of the CYP2D subfamily, and an antibody against a CYP2D isoenzyme. The profiles of these decreased metabolic activities corresponded to that of the lower metabolic activities in Dark-Agouti rats. These results indicated that a cytochrome P450 isozyme in the CYP2D subfamily was involved in E- and Z-10-hydroxylations of amitriptyline and nortriptyline in rat liver microsomes as a major isozyme in a low substrate concentration range. It seems likely that the CYP2D enzyme contributes to nortriptyline N-demethylation.