5417-98-1Relevant academic research and scientific papers
Optimization of 2-Anilino 4-Amino Substituted Quinazolines into Potent Antimalarial Agents with Oral in Vivo Activity
Gilson, Paul R.,Tan, Cyrus,Jarman, Kate E.,Lowes, Kym N.,Curtis, Joan M.,Nguyen, William,Di Rago, Adrian E.,Bullen, Hayley E.,Prinz, Boris,Duffy, Sandra,Baell, Jonathan B.,Hutton, Craig A.,Jousset Subroux, Helene,Crabb, Brendan S.,Avery, Vicky M.,Cowman, Alan F.,Sleebs, Brad E.
, p. 1171 - 1188 (2017/02/19)
Novel antimalarial therapeutics that target multiple stages of the parasite lifecycle are urgently required to tackle the emerging problem of resistance with current drugs. Here, we describe the optimization of the 2-anilino quinazoline class as antimalarial agents. The class, identified from publicly available antimalarial screening data, was optimized to generate lead compounds that possess potent antimalarial activity against P. falciparum parasites comparable to the known antimalarials, chloroquine and mefloquine. During the optimization process, we defined the functionality necessary for activity and improved in vitro metabolism and solubility. The resultant lead compounds possess potent activity against a multidrug resistant strain of P. falciparum and arrest parasites at the ring phase of the asexual stage and also gametocytogensis. Finally, we show that the lead compounds are orally efficacious in a 4 day murine model of malaria disease burden.
IMAGING AGENTS FOR NEURAL FLUX
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, (2016/02/10)
Provided herein are radiolabeled compounds useful for non-invasive imaging techniques. An exemplary radiolabeled compound provided herein is useful as a radiotracer for positron emission tomography. The present application also provides unlabeled compounds useful in methods of treating diseases of the central nervous system or disease of the peripheral nervous system. Methods for preparing radiolabeled compounds, preparing unlabeled compounds, and diagnostic methods using labeled or unlabeled compounds are also provided.
