116539-59-4

Basic information

• Product Name: Duloxetine
• Synonyms: DULOXETINE;DULOXETINE-D3;(S)-DULOXETINE;DULOXETIN;(3S)-N-methyl-3-naphthalen-1-yloxy-3-thiophen-2-yl-propan-1-amine;N-Methyl-gama-(1-naphthalenyloxy)-2-thiophenepropanamine;DULOXETINE HCI;Duloxetine & Intermediates
• CAS NO: 116539-59-4
• Molecular Formula: C₁₈H₁₉NOS
• Molecular Weight: 297.41
• EINECS: 1533716-785-6
• Product Categories: ACTIVE PHARMACEUTICAL INGREDIENTS;API
• Mol File: 116539-59-4.mol
• Article Data: 62

Chemical Properties

• Boiling Point: 466.2 °C at 760 mmHg
• Flash Point: 235.7 °C
• Appearance: /
• Density: 1.158 g/cm³
• Vapor Pressure: 7.23E-09mmHg at 25°C
• Refractive Index: 1.627
• PKA: 10.02±0.10(Predicted)
• CAS DataBase Reference: Duloxetine(CAS DataBase Reference)
• NIST Chemistry Reference: Duloxetine(116539-59-4)
• EPA Substance Registry System: Duloxetine(116539-59-4)

Safety Data

• Hazardous Substances Data: 116539-59-4(Hazardous Substances Data)

Usage

Uses

Antidepressant.

Brand name

Cymbalta (Lilly).

General Description

Duloxetine (Cymbalta) is a newer antidepressant. It islargely like venlafaxine, which is an SNERI (selective norepinephrinereuptake inhibitor).

Pharmacokinetics

Duloxetine appears to be fairly well absorbed after oral doses, with peak plasma levels in 6 to 10 hours and linear pharmacokinetics. The drug is extensively metabolized in the liver to active metabolites, with 72% of an oral dose primarily excreted in the urine as conjugated metabolites and up to 15% appearing in the feces. N-demethylation to an active metabolite (CYP2D6) and hydroxylation of the naphthyl ring (CYP1A2) at either the 4-, 5-, or 6-positions are the main metabolic pathways for duloxetine. Its metabolites are primarily excreted into the urine as glucuronide, sulfate, and O-methylated conjugation products. The major metabolites found in plasma also were found in the urine. Preclinical data for 4-hydroxyduloxetine suggests it has a similar pharmacological profile to duloxetine, with selective inhibition of SERT but less activity at the NET.

Clinical Use

Duloxetine has been approved for the treatment of depression and diabetic peripheral neuropathic pain. It is another analogue in the line of fluoxetine-based products from Lilly, in which the phenyl and phenoxy groups of fluoxetine have been respectively replaced with the benzene isostere, thiophene, and a naphthyloxy group (previously described under fluoxetine). Duloxetine exhibits dual inhibition with high affinity for the SERTs and NETs, with a five times preferential inhibition of the SERT. Duloxetine appears to be a more potent in vitro blocker of SERTs and NETs than venlafaxine. In humans, duloxetine has a low affinity for the other neuroreceptors, suggesting low incidence of unwanted adverse effects.

Drug interactions

Potentially hazardous interactions with other drugsAntibacterials: metabolism inhibited by ciprofloxacin - avoid.Anticoagulants: possibly increased risk of bleeding with dabigatran.Other CNS medication: enhanced effect.Antidepressants: avoid with MAOIs, moclobemide, St John’s wort, tryptophan, venlaflaxine, amitriptyline, clomipramine and SSRIs due to increased risk of serotonin syndrome; increased risk of side effects with tricyclic antidepressants; fluvoxamine decreases the clearance of duloxetine by 77% - avoid; possible increased risk of convulsions with vortioxetine.Antimalarials: avoid with artemether/lumefantrine and piperaquine with artenimol.Dapoxetine: avoid concomitant use.Methylthioninium: risk of CNS toxicity - avoid if possible.

Metabolism

Duloxetine is extensively metabolised and the metabolites are excreted principally in urine. Both cytochromes P450-2D6 and 1A2 catalyse the formation of the two major metabolites, glucuronide conjugate of 4-hydroxy duloxetine and sulphate conjugate of 5-hydroxy, 6-methoxy duloxetine. Based upon in vitro studies, the circulating metabolites of duloxetine are considered pharmacologically inactive

InChI:InChI=1/C18H19NOS/c1-19-12-11-17(18-10-5-13-21-18)20-16-9-4-7-14-6-2-3-8-15(14)16/h2-10,13,17,19H,11-12H2,1H3/t17-/m1/s1

Upstream product

• 164071-63-0 S-3-iodo-1-(2-thienyl)-1-(1-naphthalenyloxy)propane 
• 74-89-5 methylamine 
• 527-72-0 2-thiophenylcarboxylic acid 
• 134568-16-4 methyl 3-oxo-3-(thien-2-yl)propanoate 
• 896446-94-9 duloxetine ethyl carbamate 
• 132335-46-7 N-methyl-(S)-duloxetine 
• 136434-34-9 duloxetine hydrochloride 
• 116817-86-8 (+)-(S)-N-methyl-γ-(1-naphthyloxy)-2-thiophenepropylamine maleate 
• 321-38-0 1-Fluoronaphthalene 
• 98-03-3 thiophene-2-carbaldehyde 
• 1374030-94-0 (S)-3-(diallylamino)-1-(thiophen-2-yl)propan-1-ol 
• 39511-07-4 (E)-2-(2-thienyl)ethylene-1-carbaldehyde 
• 1620141-95-8 C₂₀H₁₇NS 
• 1124-65-8 3-(2-thienyl)-2-propenoic acid 

Downstream Products

• 116817-86-8 (+)-(S)-N-methyl-γ-(1-naphthyloxy)-2-thiophenepropylamine maleate 
• 136434-34-9 duloxetine hydrochloride 
• 116817-13-1 duloxetine 
• 1033719-36-6 2-(1-(2-hydroxynaphth-1-yl)-3-(methylamino)propyl)-thiophene hydrochloride 
• 953028-76-7 2-(1-(4-hydroxynaphth-1-yl)-3-(methylamino)propyl)-thiophene hydrochloride 
• 90-15-3 α-naphthol 
• 132335-46-7 N-methyl-(S)-duloxetine 
• 1309349-73-2 ketorolac (S)-duloxetine salt 
• 1309349-74-3 nimesulide (S)-duloxetine salt 
• 1309349-83-4 diclofenac (S)-duloxetine salt 
• 1309349-71-0 acemetacin (S)-duloxetine salt 
• 1309349-90-3 sulindac (S)-duloxetine salt 
• 949096-01-9 (+/-)-N-methyl-3-(2-thienyl)-3-(4-hydroxy-naphtyl)-propylamine hydrogenbromide 

Relevant articles and documents

Preparation method of duloxetine

To the method, 1 - naphthol and 3 - (2 - thienyl) -2 - acrolein serve as starting materials, and (S)-3 - (1 - naphthyloxy) -3 - (2 - thienyl) propanal is obtained through addition reaction under the action of a catalyst. The raw materials are cheap and easily available, and 1 - fluoronaphthalene which is expensive is not needed. Sodium hydride and operation are tedious, the cost is low, the process operation is safe and convenient, the three wastes are small in generation amount, and green and environment-friendly. The reaction atom economy is high, the reaction selectivity of each step is high, the side reaction is small, the optical purity and yield of the target product are high, and the green industrial production is facilitated.

Duloxetine hydrochloride salt of basic and duloxetine (by machine translation)

[Problem] to suppress toxic byproducts, and suppressing the formation of decomposition products of high purity optical isomers as well as the method for manufacturing a basic duloxetine hydrochloride duloxetine. [Solution] a basic manufacturing method of duloxetine, [...], potassium hydroxide and toluene in the presence of alcohol in the mixing step, and, by heating the reaction mixture obtained, comprising the step of distilling off the solvent in the reaction portion, a basic manufacturing method of duloxetine. [Drawing] no (by machine translation)

Preparation method for chiral gamma-sec-amino-alcohol

The invention provides a preparation method for chiral gamma-sec-amino-alcohol. The preparation method is characterized in that an acid addition salt of beta-sec-amino-ketone as shown in a general formula (I) which is described in the specification, alkali, a metal salt additive and a bisphosphine-rhodium complex are added into a solvent and a reaction is carried out in a hydrogen atmosphere so as to produce a chiral gamma-sec-amino-alcohol compound as shown in a general formula (II) which is described in the specification; and in the general formula (I) and the general formula (II), Ar represents an aryl group with or without substituent, R represents an alkyl group or aralkyl group, and HY represents acid. The preparation method is simple in synthesis route and process; the metal salt additive substantially improves the technical effect of rhodium in catalysis of asymmetric hydrogenation and enhances reaction yield and optical purity of the product; and production process is simplified, production cost is lowered, and the preparation method is suitable for industrial large-scale production.