34298-00-5

Upstream product

• 486-71-5 (+)-epilupinine 
• 7635-52-1 3,4,6,7,8,9-hexahydro-2H-quinolizine-1-carboxylic acid ethyl ester 
• 90642-54-9 ethyl 7-iodo-2-heptynoate 
• 90675-48-2 7-Chlor-heptin-⁽²⁾-saeure-ethylester 
• 10297-06-0 1-chloro-5-hexyne 
• 16100-91-7 cis carbethoxy-1 octahydro-1,2,3,6,7,8,9,10-4H-pyrido<1,2-a>pyridine 
• 10248-30-3 lupinine 

Downstream Products

• 10248-22-3 (+/-)-N-Lupinyl-phthalimid 
• 105532-90-9 9-epi-lupinyliden-fluorene 
• 444339-86-0 1-phenyl-2-(quinolizidin-1β-yl)ethanone 
• 927267-42-3 3,5-dimethyl-4-(octahydro-quinolizin-1-ylmethoxy)-phenylamine 
• 927267-41-2 1-(2,6-dimethyl-4-nitro-phenoxymethyl)-octahydro-quinolizine 

Relevant academic research and scientific papers

Synthesis and comparison of antiplasmodial activity of (+), (-) and racemic 7-chloro-4-(N-lupinyl)aminoquinoline

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.

2-Phenyl-3-(quinolizidin-1-yl)-5-substituted indoles as platelet antiaggregating agents

A set of ten 2-phenyl-3-(quinolizidin-1-yl)-5-substituted indoles was prepared through the Fischer cyclization of lupinyl- and epi- lupinylphenylketone 4-substituted phenylhydrazones.Compounds were tested for antiaggregating activity on human platelets activated by adenosine diphosphate (ADP), collagen and adrenaline. At 2.5 × 10-4 M concentration most compounds strongly inhibited the aggregation induced by all the agonists considered and many of them still displayed good activity at 0.625 × 10-4 M concentration. The least active (1c) and one of the most active (1d) compounds were also tested for antiaggregating activity on rabbit platelets activated by ADP, PAF and sodium arachidonate. Both the compounds were active against ADP and PAF, but only 1d inhibited the arachidonate-induced aggregation (100% at 8 × 10-6 M concentration) and increased the bleeding time in mice. The same compounds were subjected to a general pharmacological screening and found to display several activities; of particular interest was the dose dependent reduction of serum cholesterol and heparin precipitating betalipoproteins in hypercholesterolemic mice exerted by 1c, which was still significant at the oral dose of 10 mg/kg.