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Vortioxetine hydrobromide structure
Vortioxetine hydrobromide structure

Vortioxetine hydrobromide

Iupac Name:1-[2-(2,4-dimethylphenyl)sulfanylphenyl]piperazine;hydrobromide
CAS No.: 960203-27-4
Molecular Weight:379.36
Modify Date.: 2022-10-29 06:08
Introduction: Vortioxetine hydrobromide is a multimodal serotonergic agent, inhibits 5-HT1A, 5-HT1B, 5-HT3A, 5-HT7 receptor and SERT with Ki values of 15 nM, 33 nM, 3.7 nM, 19 nM and 1.6 nM, respectively. View more+
1. Names and Identifiers
1.1 Name
Vortioxetine hydrobromide
1.2 Synonyms

1-(2-((2,4-Dimethylphenyl)sulfanyl)phenyl)piperazine monohydrobromide 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine hydrobromide 1-[2-[(2,4-Dimethylphenyl)thio]phenyl]piperazine hydrobromide 1-[2-[(2,4-Dimethylphenyl)thio]phenyl]piperazinehydrobromide 1-{2-[(2,4-Dimethylphenyl)sulfanyl]phenyl}piperazine hydrobromide (1:1) Brintellix Lu AA 21004 hydrobromide Lu AA21004 (HBr) LU AA21004 HBR LU AA21004 HYDROBROMIDE Piperazine, 1-[2-[(2,4-dimethylphenyl)thio]phenyl]-, hydrobromide (1:1) UNII:TKS641KOAY Vortioxetine (hydrobromide) Vortioxetine (Lu AA21004) HBr Vortioxetine (Lu AA21004) hydrobroMide VORTIOXETINE HBR vortioxetine monohydrobromide

1.3 CAS No.
960203-27-4
1.4 CID
56843850
1.5 Molecular Formula
C18H23BrN2S (isomer)
1.6 Inchi
InChI=1S/C18H22N2S.BrH/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;1H
1.7 InChkey
VNGRUFUIHGGOOM-UHFFFAOYSA-N
1.8 Canonical Smiles
CC1=CC(=C(C=C1)SC2=CC=CC=C2N3CCNCC3)C.Br
1.9 Isomers Smiles
CC1=CC(=C(C=C1)SC2=CC=CC=C2N3CCNCC3)C.Br
2. Properties
3.1 Precise Quality
378.076538
3.1 PSA
40.57000
3.1 logP
5.21610
3. Use and Manufacturing
4.1 Definition
ChEBI: A hydrobromide obtained by combining vortioxetine with one molar equivalent of hydrobromic acid. Used for treatment of major depressive disorder. Vortioxetine hydrobromideSupplier
4. MSDS

2.Hazard identification

2.1 Classification of the substance or mixture

Acute toxicity - Oral, Category 4

Skin sensitization, Category 1

Hazardous to the aquatic environment, short-term (Acute) - Category Acute 1

Hazardous to the aquatic environment, long-term (Chronic) - Category Chronic 1

2.2 GHS label elements, including precautionary statements

Pictogram(s)
Signal word

Warning

Hazard statement(s)

H302 Harmful if swallowed

H317 May cause an allergic skin reaction

H410 Very toxic to aquatic life with long lasting effects

Precautionary statement(s)
Prevention

P264 Wash ... thoroughly after handling.

P270 Do not eat, drink or smoke when using this product.

P261 Avoid breathing dust/fume/gas/mist/vapours/spray.

P272 Contaminated work clothing should not be allowed out of the workplace.

P280 Wear protective gloves/protective clothing/eye protection/face protection.

P273 Avoid release to the environment.

Response

P301+P312 IF SWALLOWED: Call a POISON CENTER/doctor/…if you feel unwell.

P330 Rinse mouth.

P302+P352 IF ON SKIN: Wash with plenty of water/...

P333+P313 If skin irritation or rash occurs: Get medical advice/attention.

P321 Specific treatment (see ... on this label).

P362+P364 Take off contaminated clothing and wash it before reuse.

P391 Collect spillage.

Storage

none

Disposal

P501 Dispose of contents/container to ...

2.3 Other hazards which do not result in classification

none

6. Other Information
6.0 Antidepressant
Vortioxetine HBr is a new type of diaryl sulfanyl amine antidepressants developed by Japan Takeda and Denmark Lundbeck for the treatment of depression and anxiety. FDA was admitted to be on American market in September 2013 with trade name Brintellix used for the treatment of severe depression in adults and in October of the same year, the admittance application of Vortioxetine to be listed (MAA) received positive comments from European Medicines Agency (EMA) Human Medicines Products Committee (CHMP). CHMP advised to approve of Brintellix being used for the treatment of adult patients with severe depression (MDD). The EMA European Commission granted Vortioxetine the right to be sold throughout the EU in December 2013 with four dose forms,5 mg, 10 mg, 15 mg and 20 mg. Vortioxetine hydrobromide now has applied to be listed in a number of countries except in China.
Vortioxetine HBr is considered to be a new type of multi-model antidepressant. Vitro researches show that it can antagonize 5-HT3,5-HT7and 5-HT1D receptor, activate 5-HT1A receptor, partly activate 5-HT1B receptor and inhibit 5-HT from operation.
Vortioxetine is another kind of antidepressant made by Lundbeck aiming at replace Citalopram which is expired patent drug.
The pharmacological effect, indication, drug interaction, synthetic method and so on are edited by 's Yao Yao.
6.1 Vortioxetine
Vortioxetine is an oral immediate release tablet whose main active ingredient is Vortioxetine hydrobromide, which is a kind of antidepressant. Vortioxetine hydrobromide is a slightly yellowish white powder and slightly soluble in water. It is a kind of tablet with different dose forms with each piece containing Vortioxetine hydrobromide 6.335mg,12.71mg,19.065mg or 25.42mg equivalent to 5mg, 10mg, 15mg and 20mg Vortioxetine respectively. The non-active ingredients in Vortioxetine tablet include mnnitol, microcrystalline cellulose, hydroxypropylcellulose, sodium carboxymethyl starch, magnesium stearate and thin film cover made up of hydroxypropylmethylcellulose, titanium dioxide, polyethylene glycol 400, ferric oxide and iron oxide yellow.
Clinical evaluation    1. Vortioxetine has a high affinity for 5-HT. Compared with duloxetine, oxetine, it can act on 5-HT3, 5-HT1A, 5-HT7,5-HT1D and 5-HT1B receptors with high selectivity. When used to regulate emotions , the dose is small, with simple medication once a day improving patient’s compliance. The drug has less drug interactions, high selectivity and less side effects.
Vortioxetine is a new antidepressant and is considered as the most successful drug in the study of single-phase emotional disorder. The results show that Vortioxetine is a more effective antidepressant compared with placebo and can significantly increase 5-HTT possession rate. It is safer with safety  similar to venlafaxine and the incidence of adverse reactions is lower than duloxetine. Another clinical study shows that Vortioxetine can effectively reduce the probability of recurrence after treatment.
Animal experiments show that Vortioxetine has a significant effect on behavioral analysis of antidepressant activity. In a number of rat anti-anxiety models, Vortioxetine has higher anti-anxiety activity compared to other known antidepressants and still has effect on the anxiety state on which paroxetine and duloxetine. cannot work.
In summary, compared with other antidepressants, Vortioxetine has high efficacy, less adverse reactions and obvious clinical advantages.
6.2 Biological activity
Vortioxetine (Lu AA21004) HBr is a 5-hydroxytryptamine inhibitor that inhibits 5-HT1A, 5-HT1B, 5-HT3A, 5-HT7 receptors and SERT with IC50 being 15nM,33nM, 3.7nM,19nM and1.6nM.
6.3 Approval
Vortioxetine hydrobromide is an atypical antidepressant made by Lundbeck and Takeda. It was approved by the United States Federal Drug Agency and the Committee for Medicinal Products for Human Use (CHMP) on September 30, 2013 and December 27, 2013 respectively, for the treatment of major depressive disorder in adults. Vortioxetine has also been investigated as a treatment for generalized anxiety disorder.
6.4 In vitro
Lu-AA21004 inhibits recombine human CYP1A2, CYP2C9, CYP2D6 and CYP3A4 with IC50 being 40μM, 39μM, 9.8μM and 10μM respectively. Lu AA21004 is a h5-HT1B receptor agonist with EC50 being 460nM and in the whole cell detection the intrinsic activity is 22%. In vitro full-cell cAMP assay, Lu AA21004 is a functional antagonist against r5-HT7 receptor with Ki being 200nM. Lu AA21004 is a functional antagonist of r5-HT7 receptor with IC50 being 2μM.
6.5 In vivo
The clearance on rat liver and oral bioavailability of Lu-AA21004 are 7.1(L/h)/kg and 16% respectively. Lu-AA21004 is injected subcutaneously into the hippocampus of the conscious rats at 2.5mg/kg, 5mg/kg or 10 mg/ kg to increase extracellular 5-HT levels. Lu-AA21004 significantly increases the basal level of 5-HT after being injected into medial prefrontal cortex (mPFC) at the dose of 5mg/kg or 10mg/kg for 3 days.
LuAA21004 affects the Bezold-Jarisch reflection of rats, which is dose-dependent and inhibits transient bradycardia with ED50 being 0.11mg /kg. LuAA21004 is injected subcutaneously into the medial prefrontal cortex and ventral hippocampus of the rats at the dose of 2.5-10.0mg/kg to increase the levels of extracellular 5-HT, DA, and NA. LuAA21004 is injected subcutaneously into the ventral hippocampus of rats at dose of    5mg/kg to increase extracellular 5-HT levels (200%). Lu AA21004 (10mg/kg) significantly reduces pain in rats. Lu AA21004 increases the level of ACh to 224% and 204% at dose of 5 and 10mg/kg after 20min.
6.6 Uses
Vortioxetine Hydrobromide is a multimodal serotonergic agent that inhibits 5-HT1A, 5-HT1B, 5-HT3A, 5-HT7 receptor and SERT (1,2,3).
6.7 Definition
ChEBI: A hydrobromide obtained by combining vortioxetine with one molar equivalent of hydrobromic acid. Used for treatment of major depressive disorder.
6.8 Chemical Synthesis
As the picture 2 showed, we have developed a new and practical synthetic route to vortioxetine hydrobromide on a hectogram scale. Adopting commercially available materials, through simple and traditional steps, including nucleophilic substitution, catalytic hydrogenation, and cyclization of the piperazine ring, gave the final product in 63.2% yield over three steps and with 99.3% purity (HPLC). Purification methods for the intermediates involved in the route are also given.


Pic.3 A new synthetic route to vortioxetine hydrobromide
7. Computational chemical data
  • Molecular Weight: 379.36g/mol
  • Molecular Formula: C18H23BrN2S
  • Compound Is Canonicalized: True
  • XLogP3-AA: null
  • Exact Mass: 378.07653
  • Monoisotopic Mass: 378.07653
  • Complexity: 316
  • Rotatable Bond Count: 3
  • Hydrogen Bond Donor Count: 2
  • Hydrogen Bond Acceptor Count: 3
  • Topological Polar Surface Area: 40.6
  • Heavy Atom Count: 22
  • Defined Atom Stereocenter Count: 0
  • Undefined Atom Stereocenter Count: 0
  • Defined Bond Stereocenter Count: 0
  • Undefined Bond Stereocenter Count: 0
  • Isotope Atom Count: 0
  • Covalently-Bonded Unit Count: 2
  • CACTVS Substructure Key Fingerprint: AAADceB7AABAEAAAAAAAAAAAAAAAAAAAAAA8YIAAAAAAAAABQAAAHAQQAAAADAjBWAQywYPAAAiAAiRCQACCAAAhChAIiJwIZIgIYCLgkZGUIAhgkADoyAcQgEAOEAACAAAEAQAgAAQAAAgCAAAAAAAAAA==
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9. Realated Product Infomation