Rizatriptan benzoate

Base Information

• Chemical Name: Rizatriptan benzoate
• CAS No.: 145202-66-0
• Molecular Formula: C₇H₆O₂*C₁₅H₁₉N₅
• Molecular Weight: 391.473
• Hs Code.: 2933995500
• NSC Number: 758919
• UNII: WR978S7QHH
• DSSTox Substance ID: DTXSID20162937
• Wikidata: Q27292788
• NCI Thesaurus Code: C47708
• RXCUI: 237082
• ChEMBL ID: CHEMBL1201032
• Mol file: 145202-66-0.mol

Synonyms:L 705,126;L 705126;L-705,126;L-705126;Maxalt;MK 0462;MK 462;MK-0462;MK-462;N,N-dimethyl-2-(5-(1,2,4-triazol-1-ylmethyl)-1H-indole-3-yl)ethylamine;rizatriptan;rizatriptan benzoate

Chemical Property of Rizatriptan benzoate

Chemical Property:

• Appearance/Colour: White to kind of white powder
• Vapor Pressure: 2.58E-10mmHg at 25°C
• Melting Point: 178-180 ºC
• Refractive Index: 1.645
• Boiling Point: 504.8 ºC at 760 mmHg
• Flash Point: 259.1 ºC
• PSA: 87.04000
• Density: 1.21 g/cm³
• LogP: 3.29660
• Storage Temp.: -20°C Freezer
• Solubility.: H2O: ≥5mg/mL
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 6
• Exact Mass: 391.20082506
• Heavy Atom Count: 29
• Complexity: 412

Purity/Quality:

≥99.7%, ^*data from raw suppliers

Rizatriptan, Benzoate ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T
• Hazard Codes: T
• Statements: 61

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CN(C)CCC1=CNC2=C1C=C(C=C2)CN3C=NC=N3.C1=CC=C(C=C1)C(=O)O
• Recent ClinicalTrials: Efficacy and Safety of Rizatriptan-Naproxen (10/550 mg) in the Acute Treatment of Migraine
• Recent EU Clinical Trials: Etude du rizatriptan comme prémédication antalgique lors d’une pulpite irréversible.
• Recent NIPH Clinical Trials: A clinical study on efficacy of combination therapy of triptan agent and anti-epileptic drug in patients with severe migraine seizures
• Description: Known as a 5-hydroxytryptamine agonist, Rizatriptan Benzoate is the benzoate salt form of rizatriptan with anti-migraine activity, which can be used to treat the migraine headaches. It is FDA-approved to use in the treatment of acute migraine attacks with or without aura, especially taken at the first sign of a migraine headache. However, it cannot prevent future migraine attacks and it is ineffective to prevent other types of headache. The pain of migraine headaches is believed to be induced by dilated blood vessels inside the head. Rizatriptan Benzoate relieves the pain by inducing vasoconstriction, which functions as an agonist at serotonin 5-HT1B and 5-HT1D receptors. The selective receptor binding is effective to constrict cranial vessels and inhibit the transmission of nociception, thus providing relief of migraine headaches. Rizatriptan was launched for the first time as Maxalt in Mexico for the acute treatment of migraine headaches with or without aura in adults. It is the third in a new generation of triptan migraine drugs to challenge the firstgeneration product Sumatriptan from Glaxo Wellcome, after Zolmitriptan (Zeneca) and Naratriptan (Glaxo Wellcome). It can be synthetically obtained by two related routes having respectively 3 and 4 steps, both starting from 1 -(4-aminobenzyl)-l,2,4-triazole. Rizatriptan is a full 5-HT1D/1B receptor agonist retaining a significant affinity at 5-HT1A sites (pIC50 = 6.4), with a low affinity for nond-HT sites. It shows craniovascufar selectivity for human isolated middle meningeal over coronary arteries ; its effect on coronary artery constriction is significantly less than that for Sumatriptan. Rizatriptan inhibits the release of neuropeptides that cause swelling of cranial blood vessels. Rizatriptan has a good oral bioavailability (64% and 47% in rats and dogs respectively). and a rapid onset of action : the headache relief in human occurs within 30 to 45 minutes of taking 20 mg. It also relieved nausea and hypersensitivity to noise (phonophobia) and light (photophobia) that are often symptoms accompanying a migraine attack. Among at least 6 metabolites identified in humans after a single oral dose (60 mg), the major urinary metabolite was the corresponding indole-3-acetic acid. Maxalt is available as a novel oral formulation of rapidly dissolving tablets or wafers that does not require liquid for ingestion.
• Uses: Rizatriptan Benzoate is a selective serotonin 5-HTID receptor agonist and used to treat migraine (1,2,3). It is structurally derived from tryptamine. Rizatriptan Benzoate(Maxalt) is a 5-HT1 agonist triptan drug for the treatment of migraine headaches. It is believed to work by narrowing the blood vessels around the brain. Rizatriptan also reduces the substances in the body, which can also reduce headac A selective serotonin 5-HTID receptor agonist. Structurally derived from tryptamine

Technology Process of Rizatriptan benzoate

There total 15 articles about Rizatriptan benzoate 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: 98.9%

benzoic acid (65-85-0,8013-63-6) + rizatriptan (144034-80-0) → rizatriptan benzoate (145202-66-0)

Guidance literature:

rizatriptan; In ethanol; at 80 ℃; for 0.333333h;

benzoic acid; In ethanol; for 1.5h; Reflux;

Reference yield:

benzoic acid (65-85-0,8013-63-6) + rizatriptan (144034-80-0) → 3-[[3-[2-(N,N-dimethylamino)ethyl]-2-[[3-[2-(N,N-dimethylamino)ethyl]-1H-indol-5-yl]methyl]-1H-indol-5-yl]methyl]-1H-1,2,4-triazole + rizatriptan benzoate (145202-66-0)

Guidance literature:

benzoic acid; rizatriptan; In acetone; at 0 - 30 ℃; for 4.5 - 15.5h;

With potassium carbonate; In water; pH=9 - 9.5; Product distribution / selectivity;

Reference yield:

4-((1H-1,2,4-triazol-1-yl)methyl)-2-iodobenzenamine (160194-26-3) → rizatriptan benzoate (145202-66-0)

Guidance literature:

Multi-step reaction with 4 steps

1: 1.) 2 molpercent Pd(OAc)2, Na₂CO₃; 2.) HCl / 1.) DMF, 100 deg C; 2.) MeOH

2: Et₃N / tetrahydrofuran

4: 95 percent / propan-2-ol; various solvent(s)

With hydrogenchloride; palladium diacetate; sodium carbonate; triethylamine; In tetrahydrofuran; isopropyl alcohol;

DOI:10.1016/0040-4039(94)88204-5

upstream raw materials:

benzoic acid

rizatriptan

4-((1H-1,2,4-triazol-1-yl)methyl)-2-iodobenzenamine

2-[5-(1,2,4-triazol-1-ylmethyl)-1H-indol-3-yl]ethyl alcohol

Refernces

• 1、 -. "Method for preparing the advantage grips Qu Tan a benzoic acid". Paragraph 0044-0046. . Retrieved 2017/02/09.
• 2、 -. "NOVEL PROCESS". Page/Page column 7. . Retrieved 2010/10/19.