85231-15-8Relevant articles and documents
A transition metal-free approach to a regioselective total synthesis of the natural product derivative 6-methylellipticine, a potent anticancer agent
Lin, Song-Bo,Wang, Wan-Wan,Meng, Jin-Peng,Li, Xi-Wang,Wu, Jun,Sun, Xiao-Ling
supporting information, (2019/11/26)
A transition metal-free and regioselective total synthesis of 6-methylellipticine, a potent anticancer agent, was developed. This synthetic approach mainly involved two key reactions: a direct amination of multi-functional phenol via an alkylation-Smiles
Hit-to-lead evaluation of a novel class of sphingosine 1-phosphate lyase inhibitors
Dinges, Jurgen,Harris, Christopher M.,Wallace, Grier A.,Argiriadi, Maria A.,Queeney, Kara L.,Perron, Denise C.,Dominguez, Eric,Kebede, Tegest,Desino, Kelly E.,Patel, Hetal,Vasudevan, Anil
, p. 2297 - 2302 (2016/04/20)
Inhibition of sphingosine-1-phosphate lyase has recently been proposed as a potential treatment option for inflammatory disorders such as multiple sclerosis, rheumatoid arthritis, and inflammatory bowel disease. In this report we describe our hit-to-lead evaluation of the isoxazolecarboxamide 6, a high-throughput screening hit (in vitro IC50 = 1.0 μM, cell IC50 = 1.8 μM), as a novel S1P lyase inhibitor. We were able to establish basic structure-activity relationships around 6 and succeeded in obtaining X-ray structural information which enabled structure-based design. With the discovery of 28, enzyme activity was quickly improved to IC50 = 120 nM and cell potency to IC50 = 230 nM. The main liability in the established isoxazolecarboxamide hit series was determined to be metabolic stability. In particular we identified that future lead-optimization efforts to overcome this problem should focus on blocking the N-dealkylation on the secondary amine.
Novel Phosphinic Acid-Containing Thyromimetics
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Page/Page column 107, (2009/02/11)
The present invention relates to compounds of phosphonic acid-containing T3 mimetics and monoesters thereof, stereoisomers, pharmaceutically acceptable salts, co-crystals, and prodrugs thereof and pharmaceutically acceptable salts and co-crystals of the prodrugs, as well as their preparation and uses for preventing and/or treating metabolic diseases such as obesity, NASH, hypercholesterolemia and hyperlipidemia, as well as associated conditions such as atherosclerosis, coronary heart disease, impaired glucose tolerance, metabolic syndrome x and diabetes.