1334320-82-9Relevant articles and documents
Identification of 4-(Aminomethyl)-6-(trifluoromethyl)-2-(phenoxy)pyridine Derivatives as Potent, Selective, and Orally Efficacious Inhibitors of the Copper-Dependent Amine Oxidase, Lysyl Oxidase-Like 2 (LOXL2)
Rowbottom, Martin W.,Bain, Gretchen,Calderon, Imelda,Lasof, Taylor,Lonergan, David,Lai, Andiliy,Huang, Fei,Darlington, Janice,Prodanovich, Patricia,Santini, Angelina M.,King, Christopher D.,Goulet, Lance,Shannon, Kristen E.,Ma, Gina L.,Nguyen, Katherine,MacKenna, Deidre A.,Evans, Jilly F.,Hutchinson, John H.
, p. 4403 - 4423 (2017)
LOXL2 catalyzes the oxidative deamination of ε-amines of lysine and hydroxylysine residues within collagen and elastin, generating reactive aldehydes (allysine). Condensation with other allysines or lysines drives the formation of inter- and intramolecular cross-linkages, a process critical for the remodeling of the ECM. Dysregulation of this process can lead to fibrosis, and LOXL2 is known to be upregulated in fibrotic tissue. Small-molecules that directly inhibit LOXL2 catalytic activity represent a useful option for the treatment of fibrosis. Herein, we describe optimization of an initial hit 2, resulting in identification of racemic-trans-(3-((4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl)oxy)phenyl)(3-fluoro-4-hydroxypyrrolidin-1-yl)methanone 28, a potent irreversible inhibitor of LOXL2 that is highly selective over LOX and other amine oxidases. Oral administration of 28 significantly reduced fibrosis in a 14-day mouse lung bleomycin model. The (R,R)-enantiomer 43 (PAT-1251) was selected as the clinical compound which has progressed into healthy volunteer Phase 1 trials, making it the “first-in-class” small-molecule LOXL2 inhibitor to enter clinical development.
8-AMINOISOQUINOLINE CompoundS AND USES THEREOF
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Paragraph 1305; 1306, (2020/04/29)
3-Carbonylamino-8-aminoisoquinoline Compounds of formula (I): variations thereof, and their use as inhibitors of HPK1 (hematopoietic kinase 1) are described. The Compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1-dependent disorders, methods for enhancing an immune response, and methods for preparing the 3-carbonylamino-8-aminoisoquinoline Compounds.
(HETERO)ARYLAMIDE COMPOUND FOR INHIBITING PROTEIN KINASE ACTIVITY
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Paragraph 0155; 0157, (2019/10/29)
Provided are a (hetero)arylamide compound as shown in formula (I) having an inhibitory effect on protein kinase activity, a pharmaceutically acceptable salt, a stereoisomer, a solvate or hydrate thereof, a pharmaceutical composition comprising the compound or a derivative thereof, and a method for preparing the compound. The compound can be used as an irreversible inhibitor for protein kinase for preparing a plurality of drugs comprising an anti-tumour drug.
(HETERO)ARYLAMIDE COMPOUND FOR INHIBITING PROTEIN KINASE ACTIVITY
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Paragraph 0164; 0166, (2019/10/29)
Provided are a (hetero)arylamide compound as shown in formula (I) having an inhibitory effect on protein kinase activity, a pharmaceutically acceptable salt, a stereoisomer, a solvate or hydrate thereof, a pharmaceutical composition comprising the compoun
CRYSTALLINE FORMS OF A LYSYL OXIDASE-LIKE 2 INHIBITOR AND METHODS OF MAKING
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Paragraph 00372; 00373, (2018/03/28)
Described herein are crystalline forms of pharmaceutically acceptable salts of the lysyl oxidase-like 2 (LOXL2) inhibitor (3-(4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yloxy)phenyl)((3R,4R)-3-fluoro-4-hydroxypyrrolidin-1-yl)methanone. Also described are methods of making the LOXL2 inhibitor, pharmaceutical compositions and medicaments comprising the LOXL2 inhibitor, and methods of using the LOXL2 inhibitor in the treatment of conditions, diseases, or disorders associated with LOXL2 activity.
HEPATITIS B ANTIVIRAL AGENTS
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Page/Page column 222, (2013/07/05)
The present invention includes a method of inhibiting, suppressing or preventing HBV infection in an individual in need thereof, comprising administering to the individual a therapeutically effective amount of at least one compound of the invention.
Novel series of pyrrolotriazine analogs as highly potent pan-Aurora kinase inhibitors
Abraham, Sunny,Hadd, Michael J.,Tran, Lan,Vickers, Troy,Sindac, Janice,Milanov, Zdravko V.,Holladay, Mark W.,Bhagwat, Shripad S.,Hua, Helen,Ford Pulido, Julia M.,Cramer, Merryl D.,Gitnick, Dana,James, Joyce,Dao, Alan,Belli, Barbara,Armstrong, Robert C.,Treiber, Daniel K.,Liu, Gang
supporting information; scheme or table, p. 5296 - 5300 (2011/10/08)
The synthesis and SAR for a novel series of pyrrolotriazines as pan-Aurora kinase inhibitors are described. Optimization of the cyclopropane carboxamide terminus of lead compound 1 resulted in analogs with high cellular activity and improved rat PK profiles. Notably, compound 17l demonstrated tumor growth inhibition in a mouse xenograft model.
