Eletriptan

Base Information

• Chemical Name: Eletriptan
• CAS No.: 143322-58-1
• Molecular Formula: C22H26N2O2S
• Molecular Weight: 382.527
• European Community (EC) Number: 640-088-3
• UNII: 22QOO9B8KI
• DSSTox Substance ID: DTXSID9046861
• Nikkaji Number: J979.643F
• Wikipedia: Eletriptan
• Wikidata: Q415032
• NCI Thesaurus Code: C65509
• RXCUI: 231049
• Pharos Ligand ID: ZFH1VSJFLQCP
• Metabolomics Workbench ID: 42618
• ChEMBL ID: CHEMBL1510
• Mol file: 143322-58-1.mol

Synonyms:1H-Indole,3-[(1-methyl-2-pyrrolidinyl)methyl]-5-[2-(phenylsulfonyl)ethyl]-, (R)-;(R)-5-[2-(Benzenesulfonyl)ethyl]-3-[(N-methylpyrrolidin-2-yl)methyl]-1H-indole;UK 116044;Eletriptan hydrochloride;Eletriptan HBr;

Chemical Property of Eletriptan

Chemical Property:

• Appearance/Colour: yellow foam
• Vapor Pressure: 1.58E-16mmHg at 25°C
• Boiling Point: 613.4 °C at 760 mmHg
• PKA: 17.14±0.30(Predicted)
• Flash Point: 324.8 °C
• PSA: 61.55000
• Density: 1.235 g/cm³
• LogP: 4.83970
• Storage Temp.: Hygroscopic, Refrigerator, Under Inert Atmosphere
• Solubility.: DMSO (Slightly), Methanol (Slightly)
• XLogP3: 4.1
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 6
• Exact Mass: 382.17149925
• Heavy Atom Count: 27
• Complexity: 582

Purity/Quality:

98% ^*data from raw suppliers

Eletriptan ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CN1CCCC1CC2=CNC3=C2C=C(C=C3)CCS(=O)(=O)C4=CC=CC=C4
• Isomeric SMILES: CN1CCC[C@@H]1CC2=CNC3=C2C=C(C=C3)CCS(=O)(=O)C4=CC=CC=C4
• Recent ClinicalTrials: Efficacy, Safety, and Tolerability of Oral Eletriptan for Treatment of Acute Migraine
• Recent EU Clinical Trials: A randomised, double-blind, placebo- and active comparator-controlled, five parallel groups study to investigate the efficacy and safety of BI 44370 TA (50 mg, 200 mg, and 400 mg) administered orally once during an acute migraine attack of moderate or severe intensity
• Recent NIPH Clinical Trials: MATRIX(Migrainer Assess TRiptane eXamination)
• Description: Eletriptan, the seventh member of the triptan class of antimigraine drugs was launched in Switzerland for the acute treatment of migraine. The 5-step synthesis of this conformationally restricted analog of sumatriptan involves the deprotonation of 5- bromoindole with Grignard reagent at the position C3 followed by a condensation with NCbz- D-proline acid chloride to afford the key Cbz-D-prolyl intermediate. After reduction with LiAIH4, the sulfone moiety was introduced in postion 5 by a palladium cross-coupling Heck reaction using the phenylvinyl sulfone. Eletriptan is a 5-HT receptor agonist that binds to 5-HT1B, 5HT1D and 5HT1F receptors with high potency. Activation of these receptors causes constriction of extracerebral intracranial vessels, abolition of the dural extravasation and neurogenic inflammation, and inhibition of trigeminal neuronal discharge. Eletriptan was found to be the most potent agonist at the 5-HT1D receptor compared to the other triptans with pEC50 value of 9.2. In thousands of participants in clinical trials, eletriptan has acted more effectively and more rapidly than sumatriptan to relieve pain from mild to severe attacks of migraine. Eletriptan also reduced time lost for ordinary activity to patients with migraine attacks when compared to placebo and when compared to sumatriptan. Eletriptan was also superior to sumatriptan in terms of relieving functional disability, nausea, photophobia and phonophobia. Unlike other compounds of its class, eletriptan has a positive logD value, that could underlie its rapid and complete oral absorption and may be suggestive of a good brain penetration. The oral biovailability of Eletriptan is approximately 50% (14% for Sumatriptan) with a half life of 5.7h (2h for Sumatriptan). Eletriptan was well tolerated with mild to moderate adverse events including asthenia, somnolence, dizziness and nausea. Eletriptan is a new potent and fast-acting triptan for the treatment of migraine attacks.
• Uses: A serotonin 5-HTIB/ID receptor agonist. Antimigrene Eletriptan is a selective serotonin 5-HT1B and 5-HT1D receptor agonist and used to treat migraines (1,2,3).
• Therapeutic Function: Serotonin agonist
• Clinical Use: 5HT1 receptor agonist:Acute relief of migraine
• Drug interactions: Potentially hazardous interactions with other drugsAntibacterials: concentration increased by clarithromycin and erythromycin - avoid.Antidepressants: increased risk of CNS toxicity with citalopram - avoid; possibly increased serotonergic effects with duloxetine and venlafaxine; increased serotonergic effects with St John’s wort - avoidAntifungals: concentration increased by itraconazole and ketoconazole - avoid.Antivirals: concentration increased by indinavir and ritonavir - avoid.Dapoxetine: possible increased risk of serotonergic effects - avoid for 2 weeks after stopping 5HT1 agonistsErgot alkaloids: increased risk of vasospasm - avoid.

Technology Process of Eletriptan

There total 39 articles about Eletriptan 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: 99.83%

3-[[(R)-1-methyl-2-pyrrolidinyl]methyl]-5-[2-(phenyl-sulfonyl)ethyl]indole para-toluenesulfonate (1162655-06-2) → eletriptan (143322-58-1)

Guidance literature:

With ammonia; In tert-butyl methyl ether; water; at 20 - 25 ℃; pH=10 - 10.5;

Reference yield: 92.0%

(R)-5-[(2-phenylsulfonyl)ethenyl]-3-(N-methylpyrrolidine-2-ylmethyl)-1H-indole (180637-89-2) → eletriptan (143322-58-1)

Guidance literature:

With methanesulfonic acid; 5%-palladium/activated carbon; hydrogen; In water; acetone; at 25 - 35 ℃; for 0.0833333h; under 3800.26 - 4560.31 Torr;

DOI:10.1021/op3002454

Reference yield: 91.54%

(R)-5-[(2-phenylsulfonyl)ethenyl]-3-(N-methylpyrrolidine-2-ylmethyl)-1H-indole (180637-89-2) → 5-ethyl-3-{[1-methylpyrrolidin-2-yl]methyl}-1H-indole (209682-64-4) + eletriptan (143322-58-1)

Guidance literature:

With methanesulfonic acid; 5%-palladium/activated carbon; hydrogen; In water; acetone; at 25 - 30 ℃;

DOI:10.1021/op3002454

upstream raw materials:

(R)-5-[(2-phenylsulfonyl)ethenyl]-3-(N-methylpyrrolidine-2-ylmethyl)-1H-indole

methanesulfonic acid

(2R)-2-[2-(1,3-dioxan-2yl)ethyl]-1-methylpyrrolidine (2R,3R)-2,3-bis(benzyloxy)succinic acid

3-[[(R)-1-methyl-2-pyrrolidinyl]methyl]-5-[2-(phenyl-sulfonyl)ethyl]indole para-toluenesulfonate

Downstream raw materials:

eletriptan hydrobromide

3-(N-methyl-2(R)-pyrrolidinylmethyl)-5-(2-phenylsulphonylethyl)-1H-indole hydrobromide monohydrate

(1S,2R)-3-[(1-methyl-2-pyrrolidinyl)methyl]-5-[2-(phenylsulfonyl)ethyl]-N-oxide-1H-indole

(1R,2R)-3-[(1-methyl-2-pyrrolidinyl)methyl]-5-[2-(phenylsulfonyl)ethyl]-N-oxide-1H-indole

Refernces

• 1、 Paganelli, Stefano,Tassini, Riccardo,Rathod, Vikas D.,Onida, Barbara,Fiorilli, Sonia,Piccolo, Oreste. "A Low Rhodium Content Smart Catalyst for Hydrogenation and Hydroformylation Reactions". . p. 1508 - 1521. Retrieved 2020/10/15.
• 2、 -. "A synthesis method according to sets up qu tan hydrobromide". Paragraph 0059-0060. . Retrieved 2017/10/22.