Mefloquin

FLUORINECOMPOUNDS,ORGANIC - FLUORINATED AROMATIC COMPOUNDS] (Volll) Mefloquine hydrochloride [51773-92-3]... 

Of industrial significance are ethyl 4,4,4-trifluoroacetoacetate [372-31-6] methyl 4,4,4-trifluoroacetoacetate, and isopropyl 4,4,4-trifluoroacetoacetate for the production of herbicides (eg, Monsanto s Dimension) and antimalarial agents such as Roche s Mefloquin [51773-92-3] as weU as ethyl 4,4,4-trichloroacetoacetate [3702-98-5] for the production of pharmaceuticals. 

The analysis of mefloquine in blood, using packed-column sfc, a mobile phase consisting of / -pentane modified with 1% methanol and 0.15% -butylamine, and electron capture detection has been reported (92). The method compares favorably to a previously pubflshed hplc-based procedure having a detection limit of 7.5 ng/mLin 0.1 mL blood sample. 

The success of quinine inspired the search for other antimalarials. The greatest impetus for the development of synthetic dmgs came this century when the two World Wars intermpted the supply of cinchona bark to the combatants. A stmcturally related 4-quinolinemethanol is mefloquine (65, Lariam [51773-92-3]) which now serves as an effective alternative agent for chloroquine-resistant P. falciparum. This is a potent substance that requires less than one-tenth the dose of quinine to effect cures. There are some untoward side effects associated with this dmg such as gastrointestinal upset and dizziness, but they tend to be transient. Mefloquine is not recommended for use by those using beta-blockers, those whose job requires fine coordination and spatial discrimination, or those with a history of epilepsy or psychiatric disorders. A combination of mefloquine with Fansidar (a mixture of pyrimethamine and sulfadoxine) is known as Fansimef but its use is not recommended. Resistance to mefloquine has been reported even though the compound has not been in wide use. 

Quinacrine (49) is an acridine that was used extensively from the mid-1920s to the end of World War 11. It acts much like chloroquine and is reasonably effective. Because it causes the skin to turn yellow and, in high doses, causes yellow vision, the dmg is no longer in use as an antimalarial. Pyronaridine (77), a 1-azaacridine developed in China, appears to be effective against mefloquine-resistant, but not entirely against chloroquine-resistant, strains of P falciparum. 

The recently introduced antimalanal halofantrine (6) is an orally active blood schizonucide reported to be more than 95% effective in the treatment of malaria [S] Mefloquine hydrochloride (7) contmues to be useful m the prophylaxis and treatment of malaria [9]... 

Mefloquine human plasma/whole blood liq-liq extraction... 

Antiprotozoal Drugs. Figure 5 Artemisinin combination therapy (ACT) Adding a 3-days artesunate course to mefloquine cleats the parasitaemia much more rapidly (A — A). The remaining parasites are exposed to higher mefloquine levels in ACT (B) compared to mefloquine monotherapy (B (with permission White, 1997 Antimicrob Agents Chemother 41 1413-1422). 

ACTs are currently recommended artemether-lume-fantrine, artesunate + amodiaquine, artesunate + mefloquine, artesunate + sulfadoxine-pyrimethamine [1, 5]. In areas with amodiaquine and sulfadoxine-pyrimethamine resistance exceeding 20%, i.e., SE Asia, artesunate + mefloquine or artemether-lumefantrine should be used [1,5]. 

C2H3CI3O2 302-17-0) see Chloralodol Cloral betaine Diloxanide Mefloquine Thiamphenicol chlorine e ... 

C4H5F3O2 383-63-1) see Celecoxib Efavirenz Lisinopril ethyl 7,7,7-trifluoroacetoacetate (QH7F30, 372-31-6) see Mefloquine l-ethyl-6,7,8-trilluoro-l,4-dibydro-4-oxa-3-quinoIinecarb-oxylic acid... 

C5H4LiN 60573-68-4) see Zimeldine 2-pyridyimagnesium bromide (C5H4BrMgN 21970-13-8) see Mefloquine... 

The E-state indices may define chemical spaces that are relevant in similarity/ diversity search in chemical databases. This similarity search is based on atom-type E-state indices computed for the query molecule [55]. Each E-state index is converted to a z score, Z =(% -p )/0 , where is the ith E-state atomic index, p is its mean and O is its standard deviation in the entire database. The similarity was computed with the EucHdean distance and with the cosine index and the database used was the Pomona MedChem database, which contains 21000 chemicals. Tests performed for the antiinflamatory drug prednisone and the antimalarial dmg mefloquine as query molecules demonstrated that the chemicals space defined by E-state indices is efficient in identifying similar compounds from drug and drug-tike databases. 

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