631909-17-6Relevant 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
, p. 5863 - 5884 (2019)
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.
METHYLAMINE DERIVATIVES AS LYSYSL OXIDASE INHIBITORS FOR THE TREATMENT OF CANCER
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Paragraph 00837, (2017/09/08)
Provided are compounds of the Formula (I), or a pharmaceutically acceptable salt thereof, wherein W, X, Y, Z, x, R1, R2, R3, x and n are defined in the specification. The compounds are inhibitors of lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) family members (LOXL1, LOXL2, LOXL3, LOXL4) and are useful in therapy, particularly in the treatment of cancer. Also disclosed are LOX inhibitors for use in the treatment of a cancer associated with EGFR and biomarkers that predict responsiveness to a LOX inhibitor.
Novel thiophene amidines, compositions thereof, and methods of treating complement-mediated diseases and conditions
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, (2008/06/13)
Disclosed is a method for treating the symptoms of an acute or chronic disorder mediated by the classical pathway of the complement cascade, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula I or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein R1, R2, R3, R4 and R7 are defined in the specification, Z is SO or SO2, and Ar is an aromatic or heteroaromatic group as defined herein.
NOVEL THIOPHENE AMIDINES, COMPOSITIONS THEREOF, AND METHODS OF TREATING COMPLEMENT-MEDIATED DISEASES AND CONDITIONS
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Page 94-95, (2010/02/05)
Disclosed is a method for treating the symptoms of an acute or chronic disorder mediated by the classical pathway of the complement cascade, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula (I) or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein R1, R2, R3, R4 and R7 are defined in the specification, Z is SO or SO2, and Ar is an aromatic or heteroaromatic group as defined herein.
