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
Show more names
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
- Formal charge
- 0
- Complexity
- 582
Experimental & physicochemical properties
Solubility
Readily soluble as hydrobromide formulation
1.18e-03 g/L
Human Drugs
Breast Feeding; Lactation; Milk, Human; Serotonin Receptor Agonists; Serotonin 5-HT1 Receptor Agonists; Triptans; Vasoconstrictor Agents
Pharmaceuticals
Collision Cross Section
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
- pka
- 17.14 · 17.14±0.30(Predicted)
- color
- Pale Yellow to Dark Yellow
- Stability
- Hygroscopic
- InChI
- InChI=1S/C22H26N2O2S/c1-24-12-5-6-19(24)15-18-16-23-22-10-9-17(14-21(18)22)11-13-27(25,26)20-7-3-2-4-8-20/h2-4,7-10,14,16,19,23H,5-6,11-13,15H2,1H3/t19-/m1/s1
- InChIKey
- PWVXXGRKLHYWKM-LJQANCHMSA-N
- SMILES
- N1C2=C(C=C(CCS(C3=CC=CC=C3)(=O)=O)C=C2)C(C[C@H]2CCCN2C)=C1
- CAS DataBase Reference
- 143322 · 143322-58-1(CAS DataBase Reference)
- FDA UNII
- 22 QOO9B8KI · 22QOO9B8KI
- ATC code
- 2 CC06 · N02CC06
- Protein binding
- 85 % · 85%
- Excreted unchanged in urine
- 9 % · 9%
- Volume of distribution
- 2 · 2-2.5(L/kg)
- Biological half-life
- 4 · 4 / Unchanged
- Symbol(GHS)
- 7 · GHS07,GHS05
- Signal word
- Danger
- Hazard statements
- 302 · H302-H412-H318
- Precautionary statements
- 264 · P264-P270-P301+P312-P330-P501-P273-P501-P280-P305+P351+P338-P310
Safety & regulation
GHS classification
GHS Classification
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
Toxicology
Adverse Effects
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%.
Drug Induced Liver Injury
Drug-Induced Liver Injury Severity and Toxicity (DILIst)
eletriptan
DILI Negative
Oral
DOI:10.1016/j.drudis.2019.09.022
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
N02CC06
N - Nervous system
QN - Nervous system
Pharmacodynamics
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
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.
FDA Pharmacological Classification
22QOO9B8KI
ELETRIPTAN
Mechanisms of Action [MoA] - Serotonin 1b Receptor Agonists
Mechanisms of Action [MoA] - Serotonin 1d Receptor Agonists
Established Pharmacologic Class [EPC] - Serotonin-1b and Serotonin-1d Receptor Agonist
Eletriptan is a Serotonin-1b and Serotonin-1d Receptor Agonist. The mechanism of action of eletriptan is as a Serotonin 1b Receptor Agonist and Serotonin 1d Receptor Agonist.
Absorption, Distribution and Excretion
Well absorbed after oral administration with a mean absolute bioavailability of approximately 50%.
138 L
Renal cl=3.9 L/h
Uses & manufacturing
Applications
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.
Upstream & downstream products
Upstream raw materials
Downstream products
Suppliers83 total
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
Compound notes
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