Vortioxetine

Bezeichnung:Vortioxetine

CAS-Nr508233-74-7

Englisch Name:Vortioxetine

CBNumberCB62614395

SummenformelC18H22N2S

Molgewicht298.45

MOL-Datei508233-74-7.mol

Vortioxetine physikalisch-chemischer Eigenschaften

Schmelzpunkt	115-117°C
Siedepunkt	424.8±45.0 °C(Predicted)
Dichte	1.16
storage temp.	-20°C Freezer
Löslichkeit	DMSO (Slightly), Methanol (Slightly)
pka	8.85±0.10(Predicted)
Aggregatzustand	Solid
Farbe	White to Off-White
InChI	InChI=1S/C18H22N2S/c1-14-7-8-17(15(2)13-14)21-18-6-4-3-5-16(18)20-11-9-19-10-12-20/h3-8,13,19H,9-12H2,1-2H3
InChIKey	YQNWZWMKLDQSAC-UHFFFAOYSA-N
SMILES	N1(C2=CC=CC=C2SC2=CC=C(C)C=C2C)CCNCC1

Sicherheit

Giftige Stoffe Daten

508233-74-7(Hazardous Substances Data)

Gefahreninformationscode (GHS)

Vortioxetine Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
In September 2013, vortioxetine (also known as Lu AA21004) was approved in the United States for the treatment of major depressive disorder (MDD). Vortioxetine was discovered from a designed multiple ligand approach to identifying an antidepressant agent that combined SERT inhibition with 5-HT1A agonism to more rapidly desensitize 5-HT1A receptors and 5-HT3A antagonism to improve mood and cognitive function. Vortioxetine has a human SERT IC₅₀=5.4 nM, an EC₅₀=200 nM as a human 5-HT1A receptor agonist (efficacy=96%; Ki=39 nM), and an IC₅₀=12 nM as a human 5-HT3A receptor antagonist (Ki=3.7 nM). It has weak inhibition of the dopamine and norepinephrine transporters, but high affinity for the human β1-noradrenergic receptor (Ki=46 nM), human 5-HT1B receptor (Ki=33 nM, partial agonist), and the human 5-HT-7 receptor (Ki=19 nM, antagonist).
Originator
Lundbeck (Denmark)
Verwenden
Vortioxetine can be used in biological study of effectiveness of long term vortioxetine treatment of patients with major depressive disorder.
Definition
ChEBI: An N-arylpiperazine in which the aryl group is specified as 2-[(2,4-dimethylphenyl)sulfanyl]phenyl. Used (as its hydrobromide salt) for treatment of major depressive disorder.
Trademarks
Brintellix
Clinical Use
Antidepressant
Synthese
The sequence involves iterative palladium-catalyzed carbon¨C heteroatom bond formations, the first establishing the thioethereal bond between commercially available thiol (213) and o-iodobromobenzene (214) employing conditions described by Schopfer and Schlapbach. Next, Buchwald¨CHartwig conditions were employed to establish the piperazine linkage, and this was followed by subjection to warm hydrobromic acid to furnish vortioxetine hydrobromide (XXVI) in 75% yield across the entire three-step sequence.
in vitro
vortioxetine (lu aa21004) was the lead compound, displaying high affinity for recombinant human 5-ht1a (ki = 15 nm), 5-ht1b (ki = 33 nm), 5-ht3a (ki = 3.7 nm), 5-ht7 (ki = 19 nm), and noradrenergic β1 (ki = 46 nm) receptors, and sert (ki = 1.6 nm). vortioxetine displayed antagonistic properties at 5-ht3a and 5-ht7 receptors, partial agonist properties at 5-ht1b receptors, agonistic properties at 5-ht1a receptors, and potent inhibition of sert [1].
in vivo
in conscious rats, vortioxetine significantly increased extracellular 5-ht levels in the brain after acute and 3 days of treatment. following the 3-day treatment (5 or 10 mg/kg/day) sert occupancies were only 43% and 57%, respectively [1].
target
5-HT3 receptor
Arzneimittelwechselwirkung
Potentially hazardous interactions with other drugs
Antibacterials: avoid with linezolid; concentration reduced by rifampicin - consider increasing vortioxetine dose.
Antidepressants: possible increased risk of convulsions with SSRIs and, tricyclics; avoid with moclobemide; increased risk of hypertension and CNS excitation with MAOIs - avoid.
Antiepileptics: concentration possibly reduced by carbamazepine, fosphenytoin and phenytoin - consider increasing vortioxetine dose.
Antimalarials: possible increased risk of convulsions with mefloquine; avoid with artemether with lumefantrine and artenimol with piperaquine.
Antipsychotics: possible increased risk of convulsions with butyrophenones, phenothiazines and thioxanthenes.
Dopaminergics: risk of CNS excitation and hypertension with rasagiline and selegiline.
Stoffwechsel
Vortioxetine is extensively metabolised in the liver, mainly by oxidation catalysed by CYP2D6 and to a minor extent CYP3A4/5 and CYP2C9, and subsequent glucuronic acid conjugation. The major metabolite of vortioxetine is pharmacologically inactive.
Approximately two thirds of the inactive vortioxetine metabolites are excreted in the urine and approximately one third in the faeces. Only negligible amounts of vortioxetine are excreted in the faeces.
Einzelnachweise
[1] bang-andersen b, ruhland t, jørgensen m, smith g, frederiksen k, jensen kg, zhong h, nielsen sm, hogg s, mørk a, stensbøl tb. discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (lu aa21004): a novel multimodal compound for the treatment of major depressive disorder. j med chem. 2011;54(9):3206-21.
[2] theunissen el, street d, højer am, vermeeren a, van oers a, ramaekers jg. a randomized trial on the acute and steady-state effects of a new antidepressant, vortioxetine (lu aa21004), on actual driving and cognition. clin pharmacol ther. 2013;93(6):493-501.

Vortioxetine Upstream-Materialien And Downstream Produkte

Vortioxetine Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

508233-74-7, Vortioxetine Verwandte Suche:

Send Inquriy