Zolmitriptan

Base Information

• Chemical Name: Zolmitriptan
• CAS No.: 139264-17-8
• Molecular Formula: C16H21N3O2
• Molecular Weight: 287.362
• Hs Code.: 29349990
• European Community (EC) Number: 629-919-0
• NSC Number: 760383
• UNII: 2FS66TH3YW
• DSSTox Substance ID: DTXSID8045933
• Nikkaji Number: J694.097H
• Wikipedia: Zolmitriptan
• Wikidata: Q218820
• NCI Thesaurus Code: C47789
• RXCUI: 135775
• Pharos Ligand ID: ADTFHLBU6LVP
• Metabolomics Workbench ID: 42701
• ChEMBL ID: CHEMBL1185
• Mol file: 139264-17-8.mol

Synonyms:311C90;4-((3-(2-(dimethylamino)ethyl)-1H-indol-5-yl)methyl)-2-oxazolidinone;AscoTop;Flezol;zolmitriptan;Zomig;Zomigoro

Chemical Property of Zolmitriptan

Chemical Property:

• Appearance/Colour: White or kind of white powder
• Vapor Pressure: 1.03E-12mmHg at 25°C
• Melting Point: 136-141 °C
• Refractive Index: 1.619
• Boiling Point: 563.3 °C at 760 mmHg
• PKA: 9.64(at 25℃)
• Flash Point: 294.5 °C
• PSA: 57.36000
• Density: 1.217 g/cm³
• LogP: 2.25170
• Storage Temp.: Refrigerator
• Solubility.: Soluble in DMSO at 5mg/ml
• XLogP3: 2.2
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 5
• Exact Mass: 287.16337692
• Heavy Atom Count: 21
• Complexity: 375

Purity/Quality:

99.5% ^*data from raw suppliers

Zolmitriptan ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xi
• Hazard Codes: Xi,Xn
• Statements: 36/37/38-22
• Safety Statements: 26-36

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CN(C)CCC1=CNC2=C1C=C(C=C2)CC3COC(=O)N3
• Isomeric SMILES: CN(C)CCC1=CNC2=C1C=C(C=C2)C[C@H]3COC(=O)N3
• Recent ClinicalTrials: A Study to Compare the Efficacy and Safety of HB1801 to Taxotere in Advanced Non-Small Cell Lung Cancer (NSCLC)
• Recent EU Clinical Trials: A Multicenter, Double-blind, Randomized, Placebo-controlled, 4-Armed
• Recent NIPH Clinical Trials: MATRIX(Migrainer Assess TRiptane eXamination)
• Description: Zolmitriptan is a selective serotonin receptor agonist of the 1B and 1D subtypes. It is mainly used in the acute treatment of migraine attacks with or without aura and cluster headaches. Zolmitriptan takes effect through binding to human 5-HT1Band 5-HT1Dreceptors, leading to cranial blood vessel constriction and the release of sensory neuropeptides through nerve endings in the trigeminal system.
• Uses: Zolmitriptan is a serotonin 5HTID-receptor agonist and used to treat migraine (1,2,3). A Serotonin 5HTID-receptor agonist adrenergic agonist, nasal decongestant
• Clinical Use: Zomig was launched in Germany, Denmark, Sweden and the UK for use as an antimigraine agent (with and without aura). It can be prepared by three related routes of 5 to 7 steps starting from L-4-nitrophenylalanine. Zomig is a 5-HT1D/1B receptor agonist (10 fold ratio) with modest (< 100x) affinity for 5-HT1A and 5-HT1F receptors. It has no affinity for other serotonin receptors or receptors of other neurotransmitters. It has a novel dual action mechanism: centrally it acts on the trigeminal nucleus caudalis and peripherally is acts on the trigeminovascular system. Zomig was effective in treating headaches and nonheadache (photophobia, phonophobia and nausea) symptoms. It was 2-3 times more potent than sumatriptan and is metabolized to three compounds, one of which is 2-8 times more active than the parent. It caused a 40-50% decrease in headache after 1 h and a 73-77% after 4 h. There was a 30% reoccurance of headache but 90% effective treatment with a second dose. It blocks neurogenic inflammation by inhibiting release of peptides, causes vasoconstriction, and inhibits neuronal depolarization at peripheral sites in the cranium. It is 40% bioavailable and a 10 time theraputic dose showed no safety concerns.
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: quinolones possibly inhibit metabolism - reduce dose of zolmitriptan. Antidepressants: increased risk of CNS toxicity with citalopram - avoid; risk of CNS toxicity with MAOIs and moclobemide - reduce dose of zolmitriptan to max 7.5 mg; SSRIs inhibit metabolism of zolmitriptan, reduce dose with fluvoxamine; possibly increased serotonergic effects with duloxetine and venlafaxine; increased serotonergic effects with St John’s wort - avoid concomitant use. Cimetidine: inhibits metabolism of zolmitriptan; maximum dose is 5 mg. Dapoxetine: possible increased risk of serotonergic effects - avoid for 2 weeks after stopping 5HT1 agonists. Ergot alkaloids: increased risk of vasospasm. Linezolid: risk of CNS toxicity - reduce dose of zolmitriptan.

Technology Process of Zolmitriptan

There total 13 articles about Zolmitriptan which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 93.0%

→ zolmitriptan (139264-17-8,139264-24-7,139264-82-7)

Guidance literature:

Purification / work up;

Reference yield: 90.0%

(S)-3-(2-dimethylaminoethyl)-5-[2-oxo-1,3-oxazolidin-4-ylmethyl]-1H-indol-2-carboxylic acid (659738-69-9) → zolmitriptan (139264-17-8,139264-24-7,139264-82-7)

Guidance literature:

copper(II) oxide; In quinoline; at 200 ℃; for 0.333333h;

Reference yield: 77.0%

ethyl (S)-3-(2-(dimethylamino)ethyl)-5-((2-oxazolidin-4-yl)methyl)-1H-indolecarboxylate hydrochloride (868622-23-5) → zolmitriptan (139264-17-8,139264-24-7,139264-82-7)

Guidance literature:

ethyl (S)-3-(2-(dimethylamino)ethyl)-5-((2-oxazolidin-4-yl)methyl)-1H-indolecarboxylate hydrochloride; With water; sodium carbonate; for 2 - 2.5h; Heating / reflux;

With hydrogenchloride; In water; at 15 - 18 ℃; for 3h; Heating / reflux;

With sodium hydroxide; In water; at 15 - 20 ℃; pH=9.75 - 10; Product distribution / selectivity;

upstream raw materials:

formaldehyd

(S)-2-<5-<(2-oxo-1,3-oxazolidin-4-yl)methyl>-1H-indol-3-yl>ethylamine

4,4-diethoxy-N,N-dimethyl-1-butanamine

(S)-4-(4-hydrazinobenzyl)-1,3-oxazolidin-2-one hydrochloride

Downstream raw materials:

Zolmitriptan N-oxide

Refernces

• 1、 Vujjini, Satish Kumar,Mothukuri, Vivekananda Reddy,Islam, Aminul,Bandichhor, Rakeshwar,Kagga, Mukkanti,Malakondaiah, Golla China. "Synthesis of zolmitriptan and related substances". . p. 3294 - 3306. Retrieved 2013.
• 2、 -. "PROCESS FOR THE PREPARATION OF ZOLMITRIPTAN, SALTS AND SOLVATES THEREOF". Page/Page column 11. . Retrieved 2011/05/16.