Eletriptan

HCID 77993

Basic information

CAS
143322-58-1
Standard SMILES
CN1CCC[C@@H]1Cc1c[nH]c2ccc(CCS(=O)(=O)c3ccccc3)cc12
InChIKey
PWVXXGRKLHYWKM-LJQANCHMSA-N
Molecular formula
C22H26N2O2S
Average molar mass
382.5 g/mol
Monoisotopic mass
382.17149907

Overview

Eletriptan is an N-alkylpyrrolidine, that is N-methylpyrrolidine in which the pro-R hydrogen at position 2 is replaced by a {5-[2-(phenylsulfonyl)ethyl]-1H-indol-3-yl}methyl group. It has a role as a non-steroidal anti-inflammatory drug, a serotonergic agonist and a vasoconstrictor agent. It is a member of indoles, a sulfone and a N-alkylpyrrolidine. It is a conjugate base of an eletriptan(1+).

Names & identifiers

Preferred name
Eletriptan
IUPAC
5-[2-(benzenesulfonyl)ethyl]-3-[[(2R)-1-methylpyrrolidin-2-yl]methyl]-1H-indole
English name
Eletriptan
Molecular formula
C22H26N2O2S
Molecular weight
382.52

Names & synonyms

Eletriptan143322-58-1eletriptanumUK 116044UK-116044DTXSID9046861UK-116,04422QOO9B8KICHEBI:509225-[2-(benzenesulfonyl)ethyl]-3-[[(2R)-1-methylpyrrolidin-2-yl]methyl]-1H-indoleUK-116044-04 FREE BASEUK-116,044-04 FREE BASE
Show more names
RelpaxRelpax free aMine(R)-EletriptanUnii-22qoo9B8kiEletriptan Free BaseEletriptan USP/EP/BPEletriptan Impurity 6According to triptans
5-[2-(benzenesulfonyl)ethyl]-3-{[(2R)-1-methylpyrrolidin-2-yl]methyl}-1H-indoleDTXCID7026861(R)-3-((1-methyl-2-pyrrolidinyl)methyl)-5-(2-(phenylsulfonyl)ethyl)-1H-indole3-(((2R)-1-methylpyrrolidin-2-yl)methyl)-5-(2-phenylsulfonylethyl)-1H-indole3-[[(2R)-1-methylpyrrolidin-2-yl]methyl]-5-(2-phenylsulfonylethyl)-1H-indole5-(2-(benzenesulfonyl)ethyl)-3-(((2R)-1-methylpyrrolidin-2-yl)methyl)-1H-indoleRefChem:57394N02CC06

Database identifiers

CAS
143322-58-1
PubChem CID
77993
DTXSID
DTXSID9046861
ChEMBL
CHEMBL1510
ChEBI
CHEBI:50922
UNII
22QOO9B8KI
EC Number
640-088-3
Nikkaji
J979.643F

Properties

Computed structural properties

XLogP
4.1
Topological polar surface area
61.6 Ų
Hydrogen bond donors
1
Hydrogen bond acceptors
3
Rotatable bonds
6
Heavy atoms
27

Experimental & physicochemical properties

DrugsPharmaceuticals -> Listed in ZINC15
LogP3.9
Solubility · 2 items

Readily soluble as hydrobromide formulation

1.18e-03 g/L

Human Drugs · 2 items

Breast Feeding; Lactation; Milk, Human; Serotonin Receptor Agonists; Serotonin 5-HT1 Receptor Agonists; Triptans; Vasoconstrictor Agents

Pharmaceuticals

Physical DescriptionSolid
Collision Cross Section · 2 items

189.45 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

186.1 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

Physicochemical properties

Melting point
168 · 168-170C
Boiling point
613.4 · 613.4±55.0 °C(Predicted)
Density
1.235 · 1.235±0.06 g/cm3(Predicted)
storage temp.
Sealed in dry,Room Temperature
solubility
DMSO (Slightly), Methanol (Slightly)
form
Solid

Safety & regulation

GHS classification

GHS Classification · 4 items

Danger

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P264+P265, P270, P273, P280, P301+P317, P305+P354+P338, P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 29 reports by companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Hazard information

Hazard Classes and CategoriesAcute Tox. 4 (100%)

Toxicology

Adverse Effects · 1 item

Adverse events reported from eletriptan use are mostly mild, moderate, and transient. Although eletriptan is associated with nausea, dizziness, drowsiness, and coronary vasoconstriction, the most common adverse effects include a group of sensations referred to as "triptan sensations," including paresthesia, flushing, tingling, chest tightness, and neck pain. Additional effects, such as palpitations, headaches, chills, pain, hypertonia, hypoesthesia, diaphoresis, abdominal pain, including cramps, discomfort, and pressure, xerostomia, dysphagia, dyspepsia, pharyngitis, back pain, and generalized weakness, have been reported, albeit at a much lower incidence ranging from 1% to 7%.

Toxicity SummarySigns and Symptoms of Overdose
Drug Induced Liver Injury · 5 items

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

eletriptan

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

Effects During Pregnancy and Lactation◉ Summary of Use during Lactation

Safety data

Signal word
Danger
Symbol(GHS)
GHS07,GHS05
Hazard statements
H302-H412-H318
Precautionary statements
P264-P270-P301+P312-P330-P501-P273-P501-P280-P305+P351+P338-P310

Chemistry & industry

Pharmacology

ATC Code · 3 items

N02CC06

N - Nervous system

QN - Nervous system

Protein BindingPlasma protein binding is moderate and approximately 85%.
Pharmacodynamics · 1 item

Eletriptan is a selective 5-hydroxytryptamine 1B/1D receptor agonist. In the anesthetized dog, eletriptan has been shown to reduce carotid arterial blood flow, with only a small increase in arterial blood pressure at high doses. While the effect on blood flow was selective for the carotid arterial bed, decreases in coronary artery diameter were observed. Eletriptan has also been shown to inhibit trigeminal nerve activity in the rat.

Mechanism of Action · 1 item

Eletriptan binds with high affinity to 5-HT1B, 5-HT1D and 5-HT1F receptors, has modest affinity for 5-HT1A, 5-HT1E, 5-HT2B and 5-HT7 receptors, and little or no affinity for 5-HT2A, 5-HT2C, 5-HT3, 5-HT4, 5-HT5A and 5-HT6 receptors. In contrast, eletriptan displays insignificant pharmacological activity at adrenergic alpha1, alpha2, or beta; dopaminergic D1 or D2; muscarinic; or opioid receptors. While the full mechanism of action of 5-HT receptor agonists in relieving migrains is not fully elucidated, it is proposed that the activation of 5-HT1 receptors located on intracranial blood vessels leads to vasoconstriction that correlates with the relief of migraine headaches. It is also proposed that the activation of 5-HT1 receptors on sensory nerve endings in the trigeminal system leads to the inhibition of release of pro-inflammatory neuropeptides.

Biological Half-LifeThe terminal elimination half-life of eletriptan is approximately 4 hours.
Metabolism/MetabolitesIn vitro studies indicate that eletriptan is primarily metabolized by cytochrome P-450 enzyme CYP3A4. The N-demethylated metabolite of eletriptan is the only known active metabolite.

Uses & manufacturing

UsesUse (kg; approx.) in Germany (2009): >25
Use ClassificationPharmaceuticals
Applications · 4 items

DescriptionEletriptan, 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.

UsesA serotonin 5-HTIB/ID receptor agonist. Antimigrene

UsesEletriptan is a selective serotonin 5-HT1B and 5-HT1D receptor agonist and used to treat migraines (1,2,3).

General DescriptionEletriptan, introduced into the market in 2002, is the newesttriptan with highest affinity for 5-HT1B, 5-HT1D, and 5-HT1Freceptors. It is one of the most lipophilic triptans marketedto date and is well tolerated and safe across its dosing rangeof 20 to 80 mg. However, it is metabolized primarily(>90%) by CYP3A4 isozyme to its active metabolite, theN-desmethyleletriptan, which accounts for approximately10% to 20% of the plasma concentration of that observedfor parent drug. Thus, coadministration of eletriptan withpotent CYP3A4 inhibitors such as ketoconazole, itraconazole,nefazodone, troleandomycin, clarithromycin, ritonavir,and nelfinavir may require dose reduction and closer monitoringfor CNS side effects. Furthermore, becauseeletriptan and its active metabolite, N-desmethyleletriptan,are also substrates for the P-glycoprotein efflux pumps thatare responsible for their removal from the brain, coadministrationof eletriptan with a known P-glycoprotein inhibitorand/or inducer such as digoxin, diltiazem, verapamil, or St.John’s Worth would result in higher brain levels of its activemetabolite, and thus a higher rate of the CNS side effectsreported for this drug.

Suppliers83 total

北京华美互利生物化工010-56205725 · [email protected]
武汉英诺医药科技有限公司+86-027-59232304 15387063101 · [email protected]
杭州品高化工有限公司0571-87658025 · [email protected]
武汉布林科技有限公司3456065315 13260619011 · [email protected]
Henan Rane Chemical Co., Ltd.+86-18738066252 · [email protected]

Additional notes

DefinitionChEBI: Eletriptan is an N-alkylpyrrolidine, being N-methylpyrrolidine in which the pro-R hydrogen at position 2 is substituted by a {5-[2-(phenylsulfonyl)ethyl]-1H-indol-3-yl}m thyl group.

Related reactions

21 records

Compound notes

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