Identification, Design and Biological Evaluation of Heterocyclic Quinolones Targeting Plasmodium falciparum Type II NADH:Quinone Oxidoreductase (PfNDH2) was written by Leung, Suet C.;Gibbons, Peter;Amewu, Richard;Nixon, Gemma L.;Pidathala, Chandrakala;Hong, W. David;Pacorel, Benedicte;Berry, Neil G.;Sharma, Raman;Stocks, Paul A.;Srivastava, Abhishek;Shone, Alison E.;Charoensutthivarakul, Sitthivut;Taylor, Lee;Berger, Olivier;Mbekeani, Alison;Hill, Alasdair;Fisher, Nicholas E.;Warman, Ashley J.;Biagini, Giancarlo A.;Ward, Stephen A.;O’Neill, Paul M.. And the article was included in Journal of Medicinal Chemistry in 2012.Application In Synthesis of 4-(Morpholinomethyl)benzonitrile This article mentions the following:
Following a program undertaken to identify hit compounds against NADH:ubiquinone oxidoreductase (PfNDH2), a novel enzyme target within the malaria parasite Plasmodium falciparum, hit to lead optimization led to identification of CK-2-68, a mol. suitable for further development. To reduce ClogP and improve solubility of CK-2-68 incorporation of a variety of heterocycles, within the side chain of the quinolone core, was carried out, and this approach led to a lead compound SL-2-25 (I). I has IC50s in the nanomolar range vs. both the enzyme and whole cell P. falciparum (IC50 = 15 nM PfNDH2; IC50 = 54 nM (3D7 strain of P. falciparum)) with notable oral activity of ED50/ED90 of 1.87/4.72 mg/kg vs. Plasmodium berghei (NS Strain) in a murine model of malaria when formulated as a phosphate salt. Analogs in this series also demonstrate nanomolar activity against the bc1 complex of P. falciparum providing the potential added benefit of a dual mechanism of action. The potent oral activity of 2-pyridyl quinolones underlines the potential of this template for further lead optimization studies. In the experiment, the researchers used many compounds, for example, 4-(Morpholinomethyl)benzonitrile (cas: 37812-51-4Application In Synthesis of 4-(Morpholinomethyl)benzonitrile).
4-(Morpholinomethyl)benzonitrile (cas: 37812-51-4) belongs to nitriles. Nitrile compounds can be prepared by the incorporation of a cyanide source through C–C bond formation or by dehydration of primary carboxamides. Asymmetric bioreduction of nitriles is an attractive route to produce optically active nitriles as current metal-catalyzed hydrogenations tend to have low reactivity.Application In Synthesis of 4-(Morpholinomethyl)benzonitrile
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts