A novel multiple-stage antimalarial agent that inhibits protein synthesis was written by Baragana, Beatriz;Hallyburton, Irene;Lee, Marcus C. S.;Norcross, Neil R.;Grimaldi, Raffaella;Otto, Thomas D.;Proto, William R.;Blagborough, Andrew M.;Meister, Stephan;Wirjanata, Grennady;Ruecker, Andrea;Upton, Leanna M.;Abraham, Tara S.;Almeida, Mariana J.;Pradhan, Anupam;Porzelle, Achim;Martinez, Maria Santos;Bolscher, Judith M.;Woodland, Andrew;Luksch, Torsten;Norval, Suzanne;Zuccotto, Fabio;Thomas, John;Simeons, Frederick;Stojanovski, Laste;Osuna-Cabello, Maria;Brock, Paddy M.;Churcher, Tom S.;Sala, Katarzyna A.;Zakutansky, Sara E.;Jimenez-Diaz, Maria Belen;Sanz, Laura Maria;Riley, Jennifer;Basak, Rajshekhar;Campbell, Michael;Avery, Vicky M.;Sauerwein, Robert W.;Dechering, Koen J.;Noviyanti, Rintis;Campo, Brice;Frearson, Julie A.;Angulo-Barturen, Inigo;Ferrer-Bazaga, Santiago;Gamo, Francisco Javier;Wyatt, Paul G.;Leroy, Didier;Siegl, Peter;Delves, Michael J.;Kyle, Dennis E.;Wittlin, Sergio;Marfurt, Jutta;Price, Ric N.;Sinden, Robert E.;Winzeler, Elizabeth A.;Charman, Susan A.;Bebrevska, Lidiya;Gray, David W.;Campbell, Simon;Fairlamb, Alan H.;Willis, Paul A.;Rayner, Julian C.;Fidock, David A.;Read, Kevin D.;Gilbert, Ian H.. And the article was included in Nature (London, United Kingdom) in 2015.Formula: C12H14N2O This article mentions the following:
There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. Here we describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the Plasmodium parasite, with good pharmacokinetic properties and an acceptable safety profile. DDD107498 demonstrates potential to address a variety of clin. needs, including single-dose treatment, transmission blocking and chemoprotection. DDD107498 was developed from a screening program against blood-stage malaria parasites; its mol. target has been identified as translation elongation factor 2 (eEF2), which is responsible for the GTP-dependent translocation of the ribosome along mRNA, and is essential for protein synthesis. This discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery. In the experiment, the researchers used many compounds, for example, 4-(Morpholinomethyl)benzonitrile (cas: 37812-51-4Formula: C12H14N2O).
4-(Morpholinomethyl)benzonitrile (cas: 37812-51-4) belongs to nitriles. Trimerization of aromatic nitriles requires harsh reaction conditions, high temperatures, long reaction times, and pressure. Alkyl nitriles are sufficiently acidic to undergo deprotonation of the C-H bond adjacent to the CN group.Strong bases are required, such as lithium diisopropylamide and butyl lithium. The product is referred to as a nitrile anion. Formula: C12H14N2O
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts