51492-88-7Relevant academic research and scientific papers
2,4-Diarylthiazole antiprion compounds as a novel structural class of antimalarial leads
Thompson, Mark J.,Louth, Jennifer C.,Little, Susan M.,Chen, Beining,Coldham, Iain
scheme or table, p. 3644 - 3647 (2011/07/31)
A significant intersection between antimalarial and antiprion activity is well established for certain compound classes, specifically for polycyclic antimalarial agents bearing basic nitrogen-containing sidechains (e.g., chloroquine, quinacrine, mefloquine). Screening a recently reported set of antiprion compounds with such sidechains showed these 2,4-diarylthiazole based structures also possess significant antimalarial activity. Of particular note, all but one of the compounds displayed activity against a chloroquine-resistant Plasmodium falciparum strain, identifying them as interesting leads for further development in this context. In addition, three new members of the series showed superior antiprion activity compared to the earlier-reported compounds.
Improved 2,4-diarylthiazole-based antiprion agents: Switching the sense of the Amide Group at C5 leads to an increase in potency
Thompson, Mark J.,Louth, Jennifer C.,Greenwood, Gemma K.,Sorrell, Fiona J.,Knight, Sandra G.,Adams, Nathan B. P.,Chen, Beining
, p. 1476 - 1488 (2011/11/29)
Amide derivatives of 2,4-diarylthiazole-5-carboxylic acids were synthesised and tested for efficacy in a cell line model of prion disease. A number of compounds demonstrating antiprion activity were thereby identified from the screening libraries, showing improved potency and reproducibility of results relative to amide derivatives of the related 2,4-diphenyl-5-aminothiazole, which have been documented previously. Thus, 'switching' the sense of the amide bond at thiazole C5 revealed a more promising lead series of potential prion disease therapeutics. Furthermore, 3,5-diaryl-1,2,4-thiadiazoles isolated as by-products during library synthesis provided a handful of additional examples possessing an antiprion effect, thereby augmenting the set of newly identified active compounds. Evaluation of binding to cellular prion protein (PrPC) showed only weak affinities at best, suggesting that the newly identified antiprion agents do not mediate their biological effect through direct interaction with PrPC.
