Almotriptan

Base Information

• Chemical Name: Almotriptan
• CAS No.: 154323-57-6
• Molecular Formula: C17H25N3O2S
• Molecular Weight: 335.47
• Hs Code.: 2935009090
• NSC Number: 760092
• UNII: 1O4XL5SN61
• DSSTox Substance ID: DTXSID5044289
• Nikkaji Number: J1.076.916G
• Wikipedia: Almotriptan
• Wikidata: Q409729
• NCI Thesaurus Code: C65224
• RXCUI: 279645
• Pharos Ligand ID: 7WKJVHVZU8XF
• Metabolomics Workbench ID: 43185
• ChEMBL ID: CHEMBL1505
• Mol file: 154323-57-6.mol

Synonyms:Almogran;almotriptan;almotriptan malate;Axert

Chemical Property of Almotriptan

Chemical Property:

• Appearance/Colour: light yellow or white power
• Vapor Pressure: 1.13E-11mmHg at 25°C
• Melting Point: 170-172°C
• Boiling Point: 538.7 °C at 760 mmHg
• PKA: 16.92±0.30(Predicted)
• Flash Point: 279.6 °C
• PSA: 64.79000
• Density: 1.27 g/cm³
• LogP: 3.21630
• XLogP3: 1.6
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 6
• Exact Mass: 335.16674822
• Heavy Atom Count: 23
• Complexity: 483

Purity/Quality:

99% ^*data from raw suppliers

Almotriptan ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CN(C)CCC1=CNC2=C1C=C(C=C2)CS(=O)(=O)N3CCCC3
• Recent ClinicalTrials: Evaluation of the Efficacy of Almotriptan and Ubrogepant for the Acute Treatment of Migraine
• Recent EU Clinical Trials: A Randomized, Parallel-Group, Single-Attack, Open-Label Study to Evaluate the Efficacy of Almotriptan and Ubrogepant for the Acute Treatment of Migraine (ATOM).
• Description: Almotriptan was first marketed in Spain as a new medicine against acute attacks of migraine. It is the fifth agent belonging to the “triptan” class to be launched after sumatriptan, naratriptan, zolmitriptan and rizatriptan. This close structural analog of sumatriptan can be prepared in six steps from 4-nitrobenzylsulfonyl chloride with a Fischer indole synthesis as the key step. Almotriptan acts as a dual 5-HT1D/1B agonist with a 35 to 51-fold selectivity versus 5-HT1A and 5-HT7 receptors respectively as well as having insignificant affinity for the most relevant nonserotonergic receptors (K1＞1μM). Its agonistic effect on 5-HT,n receptors of trigeminal sensory neurons turns off neurogenic inflammation by inhibiting the release of neuropeptides such as calcitonin gene-related peptide, neurokinin A and substance P. Concomitantly, its action on the 5-HT1B receptors in meningeal arteries relieves the vasodilatation of these vessels associated with migraine attacks. Almotriptan causes selective concentration-dependent vasoconstriction of human meningeal and temporal arteries (with EC50 of 0.03 and 0.7 μM) compared to basilar (EC50 = 3.5 μM) and pulmonary arteries (EC50＞10μM) or rabbit mesenteric and renal arteries (EC50＞100 μM). Although it is predominantly cleared by the kidneys as unchanged drug (45%) or transformed into inactive metabolites by monoamine oxidase A (MAO-A) and CYP3A4 enzymes in the liver, almotriptan has the highest oral bioavailability (70%) of the triptans and has a half-life of 3.5 h. The therapeutic dose of 12.5 mg is well tolerated, shows a rapid onset of action (30 min) and low recurrence rate compared to sumatriptan.
• Uses: Serotonin 5HT1B /1D-receptor agonist
• Therapeutic Function: Migraine therapy
• Drug interactions: Potentially hazardous interactions with other drugs Antidepressants: increased risk of CNS toxicity with citalopram - avoid; possibly increased serotonergic effects with duloxetine or venlafaxine; increased serotonergic effects with St John’s wort - avoid. Antifungals: concentration increased by ketoconazole (increased risk of toxicity). Dapoxetine: possible increased risk of serotonergic effects - avoid for 2 weeks after stopping 5HT1 agonists. Ergot alkaloids: increased risk of vasospasm - avoid.

Technology Process of Almotriptan

There total 17 articles about Almotriptan 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: 92.0%

1-(methylsulfonyl)-pyrrolidine (51599-68-9) + 5-bromo-3-[2-(N,N-dimethylamino)ethyl]-1H-indole (17274-65-6) → almotriptan (154323-57-6)

Guidance literature:

With nickel dichloride; lithium tert-butoxide; nixantphos; In tetrahydrofuran; at 0 - 80 ℃; for 13h; Reagent/catalyst; Inert atmosphere;

Reference yield: 88.0%

formaldehyd (50-00-0,30525-89-4,61233-19-0) + 1-[[3-(2-aminoethyl)-1H-indol-5-yl]methylsulfonyl]pyrrolidine (181178-24-5) → almotriptan (154323-57-6)

Guidance literature:

With sodium tetrahydroborate; In methanol; water; at 15 ℃; for 0.5h;

DOI:10.1016/S0040-4020(00)01091-7

Reference yield: 85.0%

dimethyl amine (124-40-3) + 2-(5-((pyrrolidin-1-ylsulfonyl)methyl)-1H-indol-3-yl)ethan-1-ol (334981-30-5) → almotriptan (154323-57-6)

Guidance literature:

2-(5-((pyrrolidin-1-ylsulfonyl)methyl)-1H-indol-3-yl)ethan-1-ol; With methanesulfonyl chloride; triethylamine; In acetonitrile; for 0.333333h; Cooling with ice;

With methanesulfonyl chloride; In acetonitrile; at 20 ℃; for 0.333333h;

dimethyl amine; In acetonitrile; at 60 ℃;

upstream raw materials:

formaldehyd

1-[[3-(2-aminoethyl)-1H-indol-5-yl]methylsulfonyl]pyrrolidine

dimethyl amine

2-(5-((pyrrolidin-1-ylsulfonyl)methyl)-1H-indol-3-yl)ethan-1-ol

Downstream raw materials:

almotriptan 2-hydroxy benzoate

almotriptan malate

Refernces

• 1、 Chen, Dongsheng,Chen, Yuanyuan,Ma, Zhilong,Zou, Lei,Li, Jianqi,Liu, Yu. "One-Pot Synthesis of Indole-3-acetic Acid Derivatives through the Cascade Tsuji-Trost Reaction and Heck Coupling". . p. 6805 - 6814. Retrieved 2018/05/29.
• 2、 -. "PROCESS FOR THE PREPARATION OF 1-[[[3-[2-(DIMETHYLAMINO)ETHYL]-1H-INDOL-5-YL]METHYL]SULFONYL] PYRROLIDINE AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS". Page/Page column 20-21. . Retrieved 2010/11/03.