1292282-20-2

Upstream product

• 1292282-19-9 (S)-4-(oxiran-2-yl)-2,8-bis(trifluoromethyl)quinoline 
• 100-46-9 benzylamine 
• 1031928-53-6 2,8-bis(trifluoromethyl)-4-vinylquinoline 
• 150785-70-9 2,8-bis(trifluoromethyl)quinolin-4-yl 4-methylbenzenesulfonate 
• 35853-41-9 2,8-bis(trifluoromethyl)quinolin-4-ol 
• 35853-45-3 (2,8-bis-trifluoromethyl)-4-bromoquinoline 
• 1292282-31-5 C₁₅H₁₀ClF₆NO₂ 
• 1292282-13-3 (R)-1-[2,8-bis(trifluoromethyl)quinolin-4yl]ethane-1,2-diol 

Relevant academic research and scientific papers

4-AMINOALCOHOLQUINOLINE DERIVATIVES, ENANTIOSELECTIVE SYNTHESIS METHODS AND THE USE THEREOF

The present invention is intended to provide new antimalarial compounds with a strong antimalarial activity as well as antibacterial activity with few neurological side effects and a new enantioselective pathway to mefloquine amino-analogs allowing the access of such compounds. The present invention relates to new 4 -aminoalcohol quinoline derivatives of formula (I), as well as the synthesis methods and the uses of such derivatives. In which Y is one selected from formulae (II) to (III). In which Z is selected from formulae (IV) to (VI), and wherein R1, R2, R3, R4, R5, R6, R7 and n are as defined in the claims.

Enantioselective synthesis method of 4-aminoalcoholquinoline derivatives and the use

Mefloquine derivatives, contrary to chloroquine derivatives have not been widely studied to date. Consequently, mefloquine and its derivatives still remain very attractive synthetic targets. Although mefloquine is usually used clinically as a racemic mixture, some studies have shown that its (+)-enantiomer is more potent than the (-)-enantiomer. Moreover, the (-)-enantiomer is responsible for side effects due to reaction with the central nervous system adenosine receptors, while the (+)-enantiomer does no bind at this binding site. Recently, different libraries of racemate 4-aminoalcoholquinolines showed interesting anti-malarial activities. Herein, the present invention describes an enantiopure synthetic and straightforward route to prepare pure enantiomer 4-aminoalcoholquinoline derivatives through the 4-oxirane key-intermediate. A regioselective SN2 ring opening of this epoxide, by diverse amines, allows to obtain the corresponding (R) or (S) 4-aminoquinolines with good yields and enantiomeric excesses generally superior to 92%. The reported methodology appears suitable for the synthesis of a large number of pure enantiomer 4-aminoalcoholquinoline derivatives.

First enantioselective synthesis of 4-aminoalcohol quinoline derivatives through a regioselective SN2 epoxide opening mechanism

Mefloquine derivatives, contrary to chloroquine derivatives have not been widely studied to date. Consequently, mefloquine and its derivatives still remain very attractive synthetic targets. Although mefloquine is usually used clinically as a racemic mixture, some studies have shown that its (+)-enantiomer is more potent than the (-)-enantiomer. Moreover, the (-)-enantiomer is responsible for side effects due to reaction with the central nervous system adenosine receptors, while the (+)-enantiomer does no bind at this binding site. Recently, different libraries of racemic 4-aminoalcohol quinolines showed interesting antimalarial activities. Herein, we describe an enantiopure synthetic and straightforward route to prepare pure enantiomer 4-aminoalcohol quinoline derivatives through a 4-oxirane key-intermediate. A regioselective SN2 ring opening of this epoxide, by diverse amines, allows us to obtain the corresponding (R) or (S) 4-aminoquinolines with good yields and enantiomeric excesses generally superior to 92%. The reported methodology appears suitable for the synthesis of a large number of pure enantiomer 4-aminoalcohol quinoline derivatives.