1067187-85-2Relevant academic research and scientific papers
Dual Role of H2O2 in Palladium-Catalyzed Dioxygenation of Terminal Alkenes
Huang, Jiuzhong,Li, Jianxiao,Zheng, Jia,Wu, Wanqing,Hu, Weigao,Ouyang, Lu,Jiang, Huanfeng
supporting information, p. 3354 - 3357 (2017/07/13)
A palladium-catalyzed, environmentally friendly dioxygenation reaction of simple alkenes has been developed that enabled rapid assembly of valuable α-hydroxy ketones with high atom economy. Notably, control experiments and 18O isotope-labeling experiments established that H2O2 played a dominant dual role in this transformation.
Discovery of 2-[1-(4-Chlorophenyl)cyclopropyl]-3-hydroxy-8- (trifluoromethyl)quinoline-4-carboxylic acid (PSI-421), a P-selectin inhibitor with improved pharmacokinetic properties and oral efficacy in models of vascular injury
Huang, Adrian,Moretto, Alessandro,Janz, Kristin,Lowe, Michael,Bedard, Patricia W.,Tam, Steve,Di, Li,Clerin, Valerie,Sushkova, Natalia,Tchernychev, Boris,Tsao, Desiree H. H.,Keith Jr., James C.,Shaw, Gray D.,Schaub, Robert G.,Wang, Qin,Kaila, Neelu
supporting information; experimental part, p. 6003 - 6017 (2010/11/19)
Previously, we reported the discovery of PSI-697 (1a), a C-2 benzyl substituted quinoline salicylic acid-based P-selectin inhibitor. It is active in a variety of animal models of cardiovascular disease. Compound 1a has also been shown to be well tolerated and safe in healthy volunteers at doses of up to 1200 mg in a phase 1 single ascending dose study. However, its oral bioavailability was low. Our goal was to identify a back up compound with equal potency, increased solubility, and increased exposure. We expanded our structure-activity studies in this series by branching at the α position of the C-2 benzyl side chain and through modification of substituents on the carboxylic A-ring of the quinoline. This resulted in discovery of PSI-421 with marked improvement in aqueous solubility and pharmacokinetic properties. This compound has shown oral efficacy in animal models of arterial and venous injury and was selected as a preclinical development compound for potential treatment of such diseases as atherosclerosis and deep vein thrombosis.
Methods and Compositions for Selectin Inhibition
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Page/Page column 22, (2008/12/04)
The present teachings relate to novel compounds of formula I: wherein the constituent variables are as defined herein. Compounds of the present teachings can act as antagonists of the mammalian adhesion proteins known as selecting. Methods for treating or preventing selectin-mediated disorders are provided, which include administration of these compounds in a therapeutically effective amount.
