Absolute configuration of the enantiomers of 7-chloro-4-[[4-(diethylamino)-1-methylbutyl]amino]quinoline (chloroquine)

Enantiomeric 1,2,4‐Trioxanes Display Equivalent in vitro Antimalarial Activity Versus Plasmodium falciparum Malaria Parasites: Implications for the Molecular Mechanism of Action of the Artemisinins

“…Other enantiomeric pairs of antimalarial agents that target haemoglobin derived oxidised haem (i.e., haematin) have also been shown to express virtually the same activity against P. falciparum , in vitro. These include enantiomers of chloroquine,28, 29 benflumetol,30 halofantrine30 and mefloquine 31. Although it is widely accepted that haematin is the target for the 4‐aminoquinoline class of antimalarial, that the achiral iron species responsible for artemisinins bioactivation is also haem (reduced haematin) has been questioned by several pieces of research and discussed in detail elsewhere 5.…”

Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases

“…enantiomers (see Fig. 1) (Witiak et al 1981;Craig et al 1988;Titus 1989;Brocks et al 1992;Brocks and Mehvar 2003) with variable stereo-selective elimination (Iredale et al 1993;McLachlan et al 1993McLachlan et al , 1994Tett et al 1994;Ducharme et al 1995;Midha et al 1998;Munster et al 2002;Brocks and Mehvar 2003;de Oliveira et al 2007); (c) wide variability in the concentration profiles from sampling of blood or plasma which is possibly due to differences in the sensitivity of analytical methods and calculations of kinetic parameters, especially the terminal elimination plasma half-life (T 1/2 ) Titus 1989); (d) marked variations of plasma concentrations in relation to dosage as well as Fig. 1 The stereochemistry is important for determining the pharmacokinetics of the drug which exists as a racemic mixture of R-(-) and S(?)…”

Synthesis and optical properties of the chloroquine enantiomers and their complexes with ferriprotoporphyrin IX in aqueous solution

“…7 After reduction to diamine 5a using complex hydrides, the benzylic group was removed by hydrogenolysis to yield (R)-4-amino-1-diethylaminopentane (novoldiamine), 2 which could be converted to the (−)-(R)-CQdiphosphate by known procedures. 3,8,9…”

“…However, slight racemization occurred during their reaction sequence. 3 The CQ-enantiomers investigated in the present work were prepared following our own synthetic route starting from (S)-and (R)-pyroglutamic acid, respectively. The optical purity of the products is in accordance with the data reported by Blaschke et al 2 The synthetic enantiomers of CQ were used in the present work for complex formation with FP, which exhibited significant CD bands in the FP-Soret region near 400 nm at alkaline pH values.…”

“…−)-(R)-CQ-diphosphate. A solution of 1.24 g (5 mmol) of 5a in 80 ml methanol was treated with hydrogen in the presence of 200 mg of 10% palladium on carbon as catalyst for 10 h. The mixture was filtered through Celite and the solvent evaporated to give 640 mg of (R)-4-Amino-1-(diethylamino)-pentane as colorless oil (81%), which was directly converted to (−)-(R)-CQ according to the literature 3. 8 [␣] 20 D : −108.7°(c = 1.050, EtOH).…”