1300106-13-1Relevant articles and documents
Anti-metastatic Inhibitors of Lysyl Oxidase (LOX): Design and Structure-Activity Relationships
Leung, Leo,Niculescu-Duvaz, Dan,Smithen, Deborah,Lopes, Filipa,Callens, Cedric,McLeary, Robert,Saturno, Grazia,Davies, Lawrence,Aljarah, Mohammed,Brown, Michael,Johnson, Louise,Zambon, Alfonso,Chambers, Tim,Ménard, Delphine,Bayliss, Natasha,Knight, Ruth,Fish, Laura,Lawrence, Rae,Challinor, Mairi,Tang, Haoran,Marais, Richard,Springer, Caroline
supporting information, p. 5863 - 5884 (2019/07/04)
Lysyl oxidase (LOX) is a secreted copper-dependent amine oxidase that cross-links collagens and elastin in the extracellular matrix and is a critical mediator of tumor growth and metastatic spread. LOX is a target for cancer therapy, and thus the search for therapeutic agents against LOX has been widely sought. We report herein the medicinal chemistry discovery of a series of LOX inhibitors bearing an aminomethylenethiophene (AMT) scaffold. High-throughput screening provided the initial hits. Structure-activity relationship (SAR) studies led to the discovery of AMT inhibitors with sub-micromolar half-maximal inhibitory concentrations (IC50) in a LOX enzyme activity assay. Further SAR optimization yielded the orally bioavailable LOX inhibitor CCT365623 with good anti-LOX potency, selectivity, pharmacokinetic properties, as well as anti-metastatic efficacy.
Directed Functionalization of Cyano-Substituted Furans and Thiophenes with TMPMgCl·LiCl
Dos Santos, Fernanda M.,Batista, Jo?o H. C.,Vessecchi, Ricardo,Clososki, Giuliano C.
supporting information, p. 2795 - 2800 (2015/12/18)
A number of novel difunctionalized furans and thiophenes has been prepared by the reaction of the cyano-substituted substrates with TMPMgCl·LiCl followed by the reaction with electrophiles. The crucial metalation step takes place under mild conditions allowing the isolation of desired derivatives in reasonable to good yields.
