1074-68-6Relevant articles and documents
Molecular Basis for the N-Terminal Bromodomain-and-Extra-Terminal-Family Selectivity of a Dual Kinase-Bromodomain Inhibitor
Divakaran, Anand,Talluri, Siva K.,Ayoub, Alex M.,Mishra, Neeraj K.,Cui, Huarui,Widen, John C.,Berndt, Norbert,Zhu, Jin-Yi,Carlson, Angela S.,Topczewski, Joseph J.,Schonbrunn, Ernst K.,Harki, Daniel A.,Pomerantz, William C. K.
, p. 9316 - 9334 (2018)
As regulators of transcription, epigenetic proteins that interpret post-translational modifications to N-terminal histone tails are essential for maintaining cellular homeostasis. When dysregulated, "reader" proteins become drivers of disease. In the case of bromodomains, which recognize N-?-acetylated lysine, selective inhibition of individual bromodomain-and-extra-terminal (BET)-family bromodomains has proven challenging. We describe the >55-fold N-terminal-BET bromodomain selectivity of 1,4,5-trisubstituted-imidazole dual kinase-bromodomain inhibitors. Selectivity for the BRD4 N-terminal bromodomain (BRD4(1)) over its second bromodomain (BRD4(2)) arises from the displacement of ordered waters and the conformational flexibility of lysine-141 in BRD4(1). Cellular efficacy was demonstrated via reduction of c-Myc expression, inhibition of NF-κB signaling, and suppression of IL-8 production through potential synergistic inhibition of BRD4(1) and p38α. These dual inhibitors provide a new scaffold for domain-selective inhibition of BRD4, the aberrant function of which plays a key role in cancer and inflammatory signaling.
COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF RESPIRATORY DISEASES
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Page/Page column 75; 78; 80; 94, (2020/06/01)
The present invention relates to new compounds that are useful in the prevention or treatment of respiratory diseases, such as asthma, acute and chronic inflammatory conditions, and fibrotic diseases or conditions in which fibrosis contributes to the pathology of the condition. The invention also relates to the preparation of the compounds, and to compositions including the compounds. The present invention also relates to the use of the compounds, as well as compositions including the compounds, in treating or preventing respiratory diseases, acute and chronic inflammatory conditions, and fibrotic diseases or conditions in which fibrosis contributes to the pathology of the condition.
COMPOUNDS FOR THE TREATMENT OF RESPIRATORY DISEASES
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Page/Page column 87, (2018/11/26)
The present invention relates to new compounds that are useful in the prevention or treatment of respiratory diseases, such as asthma, to the preparation of the compounds, and to compositions including the compounds. The present invention also relates to the use of the compounds, as well as compositions including the compounds, in treating or preventing respiratory diseases.
2-IMIDAZOLYL-PYRIMIDINE SCAFFOLDS AS POTENT AND SELECTIVE INHIBITORS OF NEURONAL NITRIC OXIDE SYNTHASE
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Paragraph 0024, (2016/01/25)
Imidazolyl-pyrimidine and related compounds, as can utilize heme-iron coordination in the selective inhibition of neuronal nitric oxide synthase.
Novel 2,4-disubstituted pyrimidines as potent, selective, and cell-permeable inhibitors of neuronal nitric oxide synthase
Mukherjee, Paramita,Li, Huiying,Sevrioukova, Irina,Chreifi, Georges,Martásek, Pavel,Roman, Linda J.,Poulos, Thomas L.,Silverman, Richard B.
, p. 1067 - 1088 (2015/03/04)
Selective inhibition of neuronal nitric oxide synthase (nNOS) is an important therapeutic approach to target neurodegenerative disorders. However, the majority of the nNOS inhibitors developed are arginine mimetics and, therefore, suffer from poor bioavai
A versatile synthesis of novel pan-PIM kinase inhibitors with initial SAR study
Flanders, Yvonne,Dumas, Stephane,Caserta, Justin,Nicewonger, Robb,Baldino, Michael,Lee, Chee-Seng,Baldino, Carmen M.
supporting information, p. 3186 - 3190 (2015/06/02)
Herein, we describe the versatile synthesis of (Z)-5-((2-aminopyrimidin-4-yl)methylene)thiazolidine-2,4-dione inhibitors (1) of the PIM family of kinases. This chemistry strategy was a key element in the multi-variable optimization program with the goal of identifying high quality leads for the development of a treatment for cancer.
NEW THIENOPYRIMIDINE DERIVATIVES, A PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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Page/Page column 135, (2015/07/15)
Compounds of formula (I): wherein R1, R2, R3, R4, R5, R6, R7, R12, X, A and n are as defined in the description.
Aminopyrimidine Kinase Inhibitors
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Page/Page column 57, (2012/11/07)
Disclosed are compounds, pharmaceutical compositions containing those compounds, and uses of the compounds and compositions as modulators of casein kinase 1 (e.g., CK1γ), casein kinase 2 (CK2), Pim-1, Pim-2, Pim-3, the TGFβ pathway, the Wnt pathway, the J
Aminopyrimidine Kinase Inhibitors
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Page/Page column 67, (2011/07/06)
Disclosed are compounds, pharmaceutical compositions containing those compounds, and uses of the compounds and compositions as modulators of casein kinase 1 (e.g., CK1γ), casein kinase 2 (CK2), Pim 1, Pim2, Pim3, the TGFβ pathway, the Wnt pathway, the JAK
IMIDAZOLE-2, 4-DIONE INHIBITORS OF CASEIN KINASE 1
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Page/Page column 73; 74, (2011/09/19)
Disclosed are compounds, pharmaceutical compositions containing those compounds, and uses of the compounds and compositions as modulators of casein kinase 1 (e.g., CK1γ), the TGFβ pathway and/or the Wnt pathway. Uses are also disclosed for the treatment o
