27429-67-0Relevant academic research and scientific papers
Optimisation of 2-(N-phenyl carboxamide) triazolopyrimidine antimalarials with moderate to slow acting erythrocytic stage activity
Bailey, Brodie L.,Nguyen, William,Ngo, Anna,Goodman, Christopher D.,Gancheva, Maria R.,Favuzza, Paola,Sanz, Laura M.,Gamo, Francisco-Javier,Lowes, Kym N.,McFadden, Geoffrey I.,Wilson, Danny W.,Laleu, Beno?t,Brand, Stephen,Jackson, Paul F.,Cowman, Alan F.,Sleebs, Brad E.
, (2021/08/30)
Malaria is a devastating parasitic disease caused by parasites from the genus Plasmodium. Therapeutic resistance has been reported against all clinically available antimalarials, threatening our ability to control the disease and therefore there is an ongoing need for the development of novel antimalarials. Towards this goal, we identified the 2-(N-phenyl carboxamide) triazolopyrimidine class from a high throughput screen of the Janssen Jumpstarter library against the asexual stages of the P. falciparum parasite. Here we describe the structure activity relationship of the identified class and the optimisation of asexual stage activity while maintaining selectivity against the human HepG2 cell line. The most potent analogues from this study were shown to exhibit equipotent activity against P. falciparum multidrug resistant strains and P. knowlesi asexual parasites. Asexual stage phenotyping studies determined the triazolopyrimidine class arrests parasites at the trophozoite stage, but it is likely these parasites are still metabolically active until the second asexual cycle, and thus have a moderate to slow onset of action. Non-NADPH dependent degradation of the central carboxamide and low aqueous solubility was observed in in vitro ADME profiling. A significant challenge remains to correct these liabilities for further advancement of the 2-(N-phenyl carboxamide) triazolopyrimidine scaffold as a potential moderate to slow acting partner in a curative or prophylactic antimalarial treatment.
Potent 2′-aminoanilide inhibitors of cFMS as potential anti-inflammatory agents
Patch, Raymond J.,Brandt, Benjamin M.,Asgari, Davoud,Baindur, Nand,Chadha, Naresh K.,Georgiadis, Taxiarchis,Cheung, Wing S.,Petrounia, Ioanna P.,Donatelli, Robert R.,Chaikin, Margery A.,Player, Mark R.
, p. 6070 - 6074 (2008/03/18)
A series of 2′-aminoanilides have been identified which exhibit potent and selective inhibitory activity against the cFMS tyrosine kinase. Initial SAR studies within this series are described which examine aroyl and amino group substitutions, as well as the introduction of hydrophilic substituents on the benzene core. Compound 47 inhibits the isolated enzyme (IC50 = 0.027 μM) and blocks CSF-1-induced proliferation of bone marrow-derived macrophages (IC50 = 0.11 μM) and as such, serves as a lead candidate for further optimization studies.
