846036-96-2Relevant academic research and scientific papers
UREA COMPOUNDS AND COMPOSITIONS AS SMARCA2/BRM ATPASE INHIBITORS
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Page/Page column 32, (2020/03/05)
A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is provided that has been shown to be useful for treating a BRM-mediated and/or BRG1-mediated disease or disorder: Formula (I) wherein R1 through R6 are as defined herein.
Discovery of Orally Active Inhibitors of Brahma Homolog (BRM)/SMARCA2 ATPase Activity for the Treatment of Brahma Related Gene 1 (BRG1)/SMARCA4-Mutant Cancers
Papillon, Julien P. N.,Nakajima, Katsumasa,Adair, Christopher D.,Hempel, Jonathan,Jouk, Andriana O.,Karki, Rajeshri G.,Mathieu, Simon,M?bitz, Henrik,Ntaganda, Rukundo,Smith, Troy,Visser, Michael,Hill, Susan E.,Hurtado, Felipe Kellermann,Chenail, Gregg,Bhang, Hyo-Eun C.,Bric, Anka,Xiang, Kay,Bushold, Geoffrey,Gilbert, Tamara,Vattay, Anthony,Dooley, Julie,Costa, Emily A.,Park, Isabel,Li, Ailing,Farley, David,Lounkine, Eugen,Yue, Q. Kimberley,Xie, Xiaoling,Zhu, Xiaoping,Kulathila, Raviraj,King, Daniel,Hu, Tiancen,Vulic, Katarina,Cantwell, John,Luu, Catherine,Jagani, Zainab
, p. 10155 - 10172 (2018/11/23)
SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin subfamily A member 2 (SMARCA2), also known as Brahma homologue (BRM), is a Snf2-family DNA-dependent ATPase. BRM and its close homologue Brahma-related gene 1 (BRG1), also known as SMARCA4, are mutually exclusive ATPases of the large ATP-dependent SWI/SNF chromatin-remodeling complexes involved in transcriptional regulation of gene expression. No small molecules have been reported that modulate SWI/SNF chromatin-remodeling activity via inhibition of its ATPase activity, an important goal given the well-established dependence of BRG1-deficient cancers on BRM. Here, we describe allosteric dual BRM and BRG1 inhibitors that downregulate BRM-dependent gene expression and show antiproliferative activity in a BRG1-mutant-lung-tumor xenograft model upon oral administration. These compounds represent useful tools for understanding the functions of BRM in BRG1-loss-of-function settings and should enable probing the role of SWI/SNF functions more broadly in different cancer contexts and those of other diseases.
CHEMICAL COMPOUNDS AS H-PGDS INHIBITORS
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, (2019/01/08)
A compound of formula (I) wherein R1, R2, R3, R4, X, Y, and A are as defined herein. The compounds of the present invention are inhibitors of hematopoietic prostaglandin D synthase (H-PGDS) and can be useful in the treatment of Duchenne muscular dystrophy. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting H-PGDS activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
QUINOLONE DERIVATIVES AS FIBROBLAST GROWTH FACTOR RECEPTOR INHIBITORS
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, (2015/09/23)
Compounds that are Fibroblast Growth Factor Inhibitors (FGFR) and are therefore useful for the treatment of diseases treatable by inhibition of FGFR are disclosed. Also disclosed are pharmaceutical compositions containing such compounds and processes for
Discovery of 1-(3,3-dimethylbutyl)-3-(2-fluoro-4-methyl-5-(7-methyl-2-(methylamino)pyrido[2,3- d ]pyrimidin-6-yl)phenyl)urea (LY3009120) as a pan-RAF inhibitor with minimal paradoxical activation and activity against BRAF or RAS mutant tumor cells
Henry, James R.,Kaufman, Michael D.,Peng, Sheng-Bin,Ahn, Yu Mi,Caldwell, Timothy M.,Vogeti, Lakshminarayana,Telikepalli, Hanumaiah,Lu, Wei-Ping,Hood, Molly M.,Rutkoski, Thomas J.,Smith, Bryan D.,Vogeti, Subha,Miller, David,Wise, Scott C.,Chun, Lawrence,Zhang, Xiaoyi,Zhang, Youyan,Kays, Lisa,Hipskind, Philip A.,Wrobleski, Aaron D.,Lobb, Karen L.,Clay, Julia M.,Cohen, Jeffrey D.,Walgren, Jennie L.,McCann, Denis,Patel, Phenil,Clawson, David K.,Guo, Sherry,Manglicmot, Danalyn,Groshong, Chris,Logan, Cheyenne,Starling, James J.,Flynn, Daniel L.
, p. 4165 - 4179 (2015/06/08)
The RAS-RAF-MEK-MAPK cascade is an essential signaling pathway, with activation typically mediated through cell surface receptors. The kinase inhibitors vemurafenib and dabrafenib, which target oncogenic BRAF V600E, have shown significant clinical efficac
HETEROCYCLIC COMPOUND
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Paragraph 0389, (2015/07/15)
Provided is a compound having a superior FLAP inhibitory action and useful as a prophylactic or therapeutic agent for arteriosclerosis and the like, and a salt thereof. The present invention relates to a compound represented by the formula wherein each symbol is as defined in the present DESCRIPTION, or a salt thereof.
MULTIPLE KINASE PATHWAY INHIBITORS
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, (2014/04/17)
Kinase with inhibitory activity against kinases disposed in multiple signaling pathways and their therapeutic uses.
RAF INHIBITOR COMPOUNDS
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, (2013/09/26)
This invention provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof; pharmaceutical compositions comprising a compound of Formula (I); and use of a compound of Formula (I) for treating specified cancers.
1,6- AND 1,8-NAPHTHYRIDINES
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, (2012/07/28)
Compounds of formula and pharmaceutically acceptable salts thereof are described, as well as the pharmaceutical compositions containing said compounds and their pharmaceutically acceptable salts, and the use of said compounds and pharmaceutical compositions for the treatment, control or amelioration of proliferative diseases, including cancer, Down syndrome or early onset Alzheimer's disease.
[1,8]naphthyridin-2-ones and related compounds for the treatment of schizophrenia
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Page/Page column 98, (2010/02/10)
This invention relates to compounds of the formula 1 wherein G, D, A, Z, Q, X, Y, R1, and R4 through R7 are defined as in the specification, processes for preparing the same and intermediates used in making the same, and pharmaceutical compositions containing such compounds and their use in the treatment of central nervous system disorders and other disorders.
