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Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines
Published on: June 23, 2019
Structure-Activity Relationship Studies of the Aryl Acetamide Triazolopyridazines against
Tanner J Schubert1, Edmund Oboh1, Hannah Peek1
1Department of Chemistry, Saint Louis University, Saint Louis, Missouri 63103, United States.
Abstract:
Our previous work identified compound 1 (SLU-2633) as a potent lead compound toward the identification of a novel treatment for cryptosporidiosis, caused by the parasite Cryptosporidium (EC50 = 0.17 μM). While this compound is potent and orally efficacious, the mechanism of action and biological target(s) of this series are currently unknown. In this study, we synthesized 70 compounds to develop phenotypic structure-activity relationships around the aryl "tail" group. In this process, we found that 2-substituted compounds are inactive, confirmed that electron withdrawing groups are preferred over electron donating groups, and that fluorine plays a remarkable role in the potency of these compounds. The most potent compound resulting from this work is SLU-10482 (52, EC50 = 0.07 μΜ), which was found to be orally efficacious with an ED90 < 5 mg/kg BID in a Cryptosporidium-infection mouse model, superior to SLU-2633.
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