(-)-Mefloquine

Base Information

• Chemical Name: (-)-Mefloquine
• CAS No.: 53230-10-7
• Deprecated CAS: 68682-27-9
• Molecular Formula: C₁₇H₁₆F₆N₂O
• Molecular Weight: 378.317
• UNII: TML814419R
• DSSTox Substance ID: DTXSID4037168,DTXSID101019853
• Nikkaji Number: J238.632A
• Wikipedia: Mefloquine
• Wikidata: Q27084116
• NCI Thesaurus Code: C61827
• RXCUI: 6694
• Pharos Ligand ID: HLVQHPYN9CJ6
• Metabolomics Workbench ID: 62894
• ChEMBL ID: CHEMBL172
• Mol file: 53230-10-7.mol

Synonyms:Lariam;Mefloquine;Mefloquine Hydrochloride;Mephloquine;Ro 21 5998 001;Ro-21-5998-001;Ro215998001;WR 142,490;WR 177,602;WR-142,490;WR-177,602;WR142,490;WR177,602

Chemical Property of (-)-Mefloquine

Chemical Property:

• Vapor Pressure: 1.18E-07mmHg at 25°C
• Melting Point: 242-244oC
• Refractive Index: 1.519
• Boiling Point: 415.7 °C at 760 mmHg
• PKA: pKa 8.6 (Uncertain)
• Flash Point: 205.2 °C
• PSA: 45.15000
• Density: 1.383g/cm³
• LogP: 4.77670
• Storage Temp.: Refrigerator, Under Inert Atmosphere
• XLogP3: 3.6
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 2
• Exact Mass: 378.11668211
• Heavy Atom Count: 26
• Complexity: 483

Purity/Quality:

98%,99%, ^*data from raw suppliers

MefloquineHCl ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antimalarial Agents
• Canonical SMILES: C1CCNC(C1)C(C2=CC(=NC3=C2C=CC=C3C(F)(F)F)C(F)(F)F)O
• Isomeric SMILES: C1CCN[C@H](C1)[C@H](C2=CC(=NC3=C2C=CC=C3C(F)(F)F)C(F)(F)F)O
• Recent ClinicalTrials: Temozolomide, Memantine Hydrochloride, Mefloquine, and Metformin Hydrochloride in Treating Patients With Glioblastoma Multiforme After Radiation Therapy
• Recent EU Clinical Trials: Pilot study to evaluate the efficacy and safety of mefloquine as prophylaxis in people exposed to the disease caused by the SARS-CoV-2 coronavirus (COVID-19)
• Recent NIPH Clinical Trials: The efficacy and safety of mefloquine in patients with progressive multifocal leukoencephalopathy
• Indications: Treatment and prophylaxis against chloroquine resistant P. falciparum malaria. Mefloquine (Lariam) is a 4-quinolinemethanol derivative used both prophylactically and acutely against resistant P. falciparum malaria. It is ineffective against the liver stage of P. vivax malaria. While its detailed mechanism of action is unknown, it is an effective blood schizonticide; that is, it acts against the form of the parasite responsible for clinical symptoms. Orally administered mefloquine is well absorbed and has an absorption half-life of about 2 hours; the elimination half-life is 2 to 3 weeks. Among its side effects are vertigo, visual alterations, vomiting, and such CNS disturbances as psychosis, hallucinations, confusion, anxiety, and depression. It should not be used concurrently with compounds known to alter cardiac conduction or prophylactically in patients operating dangerous machinery. It should not used to treat severe malaria, as there is no intravenous formulation.
• Description: Mefloquine, which was synthesized with the intent of blocking the site of metabolism in quinine with the chemically stable CF3 group, exists as four optical isomers of nearly equal activity. The drug is active against chloroquine-resistant strains of plasmodium, yet cross-resistance is not uncommon. Metabolism is cited as the possible mechanism of resistance. Mefloquine is slowly metabolized through CYP3A4 oxidation to its major inactive metabolite, carboxymefloquine. Most of the parent drug is excreted unchanged into the urine. Its coadministration with CYP3A4 inhibitors (e.g., ketoconazole) has increased the area under the curve for mefloquine by inhibiting its metabolism to carboxymefloquine.
• Uses: Mefloquine is an analog of quinine, and it differs from it in that the side chain at C4 of the quinoline ring contains a piperidine fragment instead of a quinuclidine fragment, and positions C2 and C8 are substituted with trifluoromethyl groups. This antimalarial drug was created to treat and prevent chloroquine resistance of malarial forms caused by P. falciparum. It is not clinically active against exoerythrocyte forms of P. vivax, although it is extremely active against blood schizontosides P. vivax and P. falciparum. It is intended to be used for treating weak and moderate forms of malaria caused by the indicated plasmodia. A synonym of this drug is lariam. Labelled quinoline methanol antimalarial agent. Mefloquine is also a 4-aminoquinoline. It is a blood schizonticide active against the asexual stages of all malaria parasites. Mefloquine is currently the prophylactic agent of choice for short-term travellers. Resistance of P. falciparum against mefloquine has occurred in South-East Asia. Only an oral formulation of mefloquine exists because of intense local irritation with parenteral use. It is well absorbed orally and notwithstanding a high protein binding of about 98% it is distributed throughout the body. Mefloquine is metabolized in the liver and eliminated slowly, mainly in bile and faeces with an elimination half-life of 10–30 days. Adverse effects include gastrointestinal pain and other disturbances and also, sinus bradycardia. More serious are CNS effects like dizziness and vertigo and more rarely neuropsychiatric disturbances, seizures.
• Therapeutic Function: Antimalarial
• Clinical Use: Antimalarial prophylaxis in areas of chloroquine resistance Treatment of uncomplicated multidrug-resistant malaria A mefloquine–artesunate co-formulation is available. Mefloquine has been used for the treatment of cutaneous leishmaniasis in South America.

Technology Process of (-)-Mefloquine

There total 25 articles about (-)-Mefloquine 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: 93.0%

C17H14F6N2O*2C12H10O3S → mefloquine (49752-90-1,51688-68-7,51742-87-1,53230-10-7,58737-31-8,68682-27-9,147368-41-0,148690-80-6)

Guidance literature:

With sodium tetrahydroborate; cerium(III) chloride heptahydrate; In ethanol; at 0 ℃; for 5h;

DOI:10.1002/anie.201811289

Reference yield: 91.0%

2-(4-((2S,3S)-3-(2,8-bis(trifluoromethyl)quinolin-4-yl)oxiran-2-yl)butyl)isoindoline-1,3-dione → mefloquine (49752-90-1,51688-68-7,51742-87-1,53230-10-7,58737-31-8,68682-27-9,147368-41-0,148690-80-6)

Guidance literature:

With ethanol; hydrazine hydrate; for 2h; Reflux;

DOI:10.1002/anie.201507304

Reference yield: 89.0%

(+)-(11S,12R)-erythro-mefloquine, O,O-(-)-di-p-toluoyl-L-tartrate (705291-21-0) → mefloquine (49752-90-1,51688-68-7,51742-87-1,53230-10-7,58737-31-8,68682-27-9,147368-41-0,148690-80-6)

Guidance literature:

With sodium hydroxide; In methanol; water; at 20 ℃; for 3.5h; pH=14;

upstream raw materials:

tert-butyl (S)-2-((R)-(2,8-bis(trifluoromethyl)quinolin-4-yl)(hydroxy)methyl)-5,6-dihydropyridine-1(2H)-carboxylate

(S)-tert-butyl 2-((R)-(2,8-bis(trifluoromethyl)quinolin-4-yl)(hydroxy)methyl)piperidine-1-carboxylate

(+)-(11S,12R)-erythro-mefloquine, O,O-(-)-di-p-toluoyl-L-tartrate

2,8-bis(trifluoromethyl)quinolin-4-ol

Downstream raw materials:

(R)-2-((S)-(2,8-bis(trifluoromethyl)quinolin-4-yl)(hydroxy)methyl)piperidin-1-ium chloride

(R)-tert-butyl 2-((S)-(2,8-bis(trifluoromethyl)quinolin-4-yl)(hydroxy)methyl)piperidine-1-carboxylate

(+)-(11S,12R)-erythro-mefloquine-(R)-mosher amide

(2,8-bis-trifluoromethyl-quinolin-4-yl)-piperidin-2-yl-methanol; hydrochloride

Refernces

• 1、 Engwerda, Anthonius H. J.,Maassen, Rick,Tinnemans, Paul,Meekes, Hugo,Rutjes, Floris P. J. T.,Vlieg, Elias. "Attrition-Enhanced Deracemization of the Antimalaria Drug Mefloquine". supporting information. p. 1670 - 1673. Retrieved 2019/01/04.
• 2、 Rastelli, Ettore J.,Coltart, Don M.. "A Concise and Highly Enantioselective Total Synthesis of (+)-anti- and (-)-syn-Mefloquine Hydrochloride: Definitive Absolute Stereochemical Assignment of the Mefloquines". . p. 14070 - 14074. Retrieved 2016/01/25.