2216-17-3Relevant articles and documents
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.
Zinc Chloride Complexes with Aliphatic and Aromatic Guanidine Hybrid Ligands and Their Activity in the Ring-Opening Polymerisation of d,l-Lactide
Metz, Angela,Plothe, Ramona,Glowacki, Britta,Koszalkowski, Andreas,Scheckenbach, Michael,Beringer, Andreas,R?sener, Thomas,Michaelis de Vasconcellos, Janna,Haase, Roxana,Fl?rke, Ulrich,Hoffmann, Alexander,Herres-Pawlis, Sonja
, p. 4974 - 4987 (2016/11/09)
The synthesis of the new hybrid guanidine ligands DMEGdmap, DMEGdeae, TMGdmab, DMEGdmab, TMGdeab and DMEGdeab is reported. These ligands were combined with zinc chloride, and the six obtained new complexes were structurally characterised by X-ray crystall
Synthesis of benzimidazoles via iridium-catalyzed acceptorless dehydrogenative coupling
Sun, Xiang,Lv, Xiao-Hui,Ye, Lin-Miao,Hu, Yu,Chen, Yan-Yan,Zhang, Xue-Jing,Yan, Ming
supporting information, p. 7381 - 7383 (2015/07/15)
Iridium-catalyzed acceptorless dehydrogenative coupling of tertiary amines and arylamines has been developed. A number of benzimidazoles were prepared in good yields. An iridium-mediated C-H activation mechanism is suggested. This finding represents a novel strategy for the synthesis of benzimidazoles.