10248-22-3Relevant articles and documents
SYNTHESIS, CRYSTAL STRUCTURE, AND STABILITY OF N-LUPINYLPHTHALIMIDE CONFORMERS
Fazylov, S. D.,Makhmutova, A. S.,Nurkenov, O. A.,Nurmaganbetov, Zh. S.,Satpaeva, Zh. B.,Turdybekov, D. M.,Turdybekov, K. M.
, p. 1823 - 1826 (2020/12/28)
Abstract: As a result of studying the interaction of chlorolupinine with potassium phthalimide, the optimal synthesis conditions for N-lupinylphthalimide by the Gabriel method are identified. The crystal structure of N-lupinylphthalimide is determined for the first time by single crystal XRD. The energy characteristics are calculated using the quantum chemical method. It is found that the conformer with the chair conformation of the cycles with the axial orientation of the phthalimide substituent is more stable than that with the equatorial orientation.
Synthesis and comparison of antiplasmodial activity of (+), (-) and racemic 7-chloro-4-(N-lupinyl)aminoquinoline
Rusconi, Chiara,Vaiana, Nadia,Casagrande, Manolo,Basilico, Nicoletta,Parapini, Silvia,Taramelli, Donatella,Romeo, Sergio,Sparatore, Anna
, p. 5980 - 5985 (2012/11/06)
Recently the N-(-)-lupinyl-derivative of 7-chloro-4-aminoquinoline ((-)-AM-1; 7-chloro-4-{N-[(1S,9aR)(octahydro-2H-quinolizin-1-yl)methyl]amino} quinoline) showed potent in vitro and in vivo activity against both Chloroquine susceptible and resistant strains of Plasmodium falciparum. However, (-)-AM-1 is synthesized starting from (-)-lupinine, an expensive alkaloid isolated from Lupinus luteus whose worldwide production is not sufficient, at present, for large market purposes. To overcome this issue, the corresponding racemic compound, derived from synthetic (±)-lupinine was considered a cheaper alternative for the development of a novel antimalarial agent. Therefore, the racemic and the 7-chloro-4-(N-(+)-lupinyl)aminoquinoline ((±)-AM-1; (+)-AM-1) were synthesized and their in vitro antimalarial activity and cytotoxicity compared with those of (-)-AM-1. The (+)-lupinine required for the synthesis of (+)-AM-1 was obtained through a not previously described lipase catalyzed kinetic resolution of (±)-lupinine. In terms of antimalarial activity, (±)-AM1 and (+)-AM1 demonstrated very good activity in vitro against both CQ-R and CQ-S strains of P. falciparum (range IC50 16-35 nM), and low toxicity against human normal cell lines (therapeutic index >1000), comparable with that of (-)-AM1. These results confirm that the racemate (±)-AM1 could be considered as a potential antimalarial agent, ensuring a decrease of costs of synthesis compared to (-)-AM1.
