Oboh, Edmund published the artcileOptimization of the Urea Linker of Triazolopyridazine MMV665917 Results in a New Anticryptosporidial Lead with Improved Potency and Predicted hERG Safety Margin, Computed Properties of 73874-95-0, the main research area is triazolo pyridazine derivative structure linker preparation cryptosporidiosis.
Cryptosporidiosis is caused by infection of the small intestine by Cryptosporidium parasites, resulting in severe diarrhea, dehydration, malabsorption, and potentially death. The only FDA-approved therapeutic is only partially effective in young children and ineffective for immunocompromised patients. Triazolopyridazine MMV665917 is a previously reported anti-Cryptosporidium screening hit with in vivo efficacy but suffers from modest inhibition of the hERG ion channel, which could portend cardiotoxicity. Herein, we describe our initial development of structure-activity relationships of this novel lead series with a particular focus on optimization of the piperazine-urea linker. We have discovered that piperazine-acetamide is a superior linker resulting in identification of SLU-2633, which has an EC50 of 0.17μM, an improved projected margin vs. hERG, prolonged pharmacokinetic exposure in small intestine, and oral efficacy in vivo with minimal systemic exposure. SLU-2633 represents a significant advancement toward the identification of a new effective and safe treatment for cryptosporidiosis.
Journal of Medicinal Chemistry published new progress about Coccidiostats. 73874-95-0 belongs to class piperidines, name is tert-Butyl piperidin-4-ylcarbamate, and the molecular formula is C10H20N2O2, Computed Properties of 73874-95-0.
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem