886008-57-7Relevant academic research and scientific papers
Substituted Pyridazin-3(2 H)-ones as Highly Potent and Biased Formyl Peptide Receptor Agonists
Deora, Girdhar Singh,Qin, Cheng Xue,Vecchio, Elizabeth A.,Debono, Aaron J.,Priebbenow, Daniel L.,Brady, Ryan M.,Beveridge, Julia,Teguh, Silvia C.,Deo, Minh,May, Lauren T.,Krippner, Guy,Ritchie, Rebecca H.,Baell, Jonathan B.
supporting information, p. 5242 - 5248 (2019/05/28)
Herein we describe the development of a focused series of functionalized pyridazin-3(2H)-one-based formyl peptide receptor (FPR) agonists that demonstrate high potency and biased agonism. The compounds described demonstrated biased activation of prosurvival signaling, ERK1/2 phosphorylation, through diminution of the detrimental FPR1/2-mediated intracellular calcium (Cai2+) mobilization. Compound 50 showed an EC50 of 0.083 μM for phosphorylation of ERK1/2 and an approximate 20-fold bias away from Cai2+ mobilization at the hFPR1.
Structure-activity relationship study of selective benzimidazole-based inhibitors of Cryptosporidium parvum IMPDH
Kirubakaran, Sivapriya,Gorla, Suresh Kumar,Sharling, Lisa,Zhang, Minjia,Liu, Xiaoping,Ray, Soumya S.,MacPherson, Iain S.,Striepen, Boris,Hedstrom, Lizbeth,Cuny, Gregory D.
scheme or table, p. 1985 - 1988 (2012/04/05)
Cryptosporidium parasites are important waterborne pathogens of both humans and animals. The Cryptosporidium parvum and Cryptosporidium hominis genomes indicate that the only route to guanine nucleotides is via inosine 5′-monophosphate dehydrogenase (IMPDH). Thus the inhibition of the parasite IMPDH presents a potential strategy for treating Cryptosporidium infections. A selective benzimidazole-based inhibitor of C. parvum IMPDH (CpIMPDH) was previously identified in a high throughput screen. Here we report a structure-activity relationship study of benzimidazole-based compounds that resulted in potent and selective inhibitors of CpIMPDH. Several compounds display potent antiparasitic activity in vitro.
