- Rational Design and Synthesis of Selective PRMT4 Inhibitors: A New Chemotype for Development of Cancer Therapeutics**
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Protein arginine N-methyl transferase 4 (PRMT4) asymmetrically dimethylates the arginine residues of histone H3 and nonhistone proteins. The overexpression of PRMT4 in several cancers has stimulated interest in the discovery of inhibitors as biological tools and, potentially, therapeutics. Although several PRMT4 inhibitors have been reported, most display poor selectivity against other members of the PRMT family of methyl transferases. Herein, we report the structure-based design of a new class of alanine-containing 3-arylindoles as potent and selective PRMT4 inhibitors, and describe key structure–activity relationships for this class of compounds.
- Sutherland, Mathew,Li, Alice,Kaghad, Anissa,Panagopoulos, Dimitrios,Li, Fengling,Szewczyk, Magdalena,Smil, David,Scholten, Cora,Bouché, Léa,Stellfeld, Timo,Arrowsmith, Cheryl H.,Barsyte, Dalia,Vedadi, Masoud,Hartung, Ingo V.,Steuber, Holger,Britton, Robert,Santhakumar, Vijayaratnam
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supporting information
p. 1116 - 1125
(2021/03/08)
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- Synthesis, pharmacological evaluation and QSAR modeling of mono-substituted 4-phenylpiperidines and 4-phenylpiperazines
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A series of mono-substituted 4-phenylpiperidines and -piperazines have been synthesized and their effects on the dopaminergic system tested in vivo. The structure activity relationship (SAR) revealed that the position and physicochemical character of the
- Pettersson, Fredrik,Svensson, Peder,Waters, Susanna,Waters, Nicholas,Sonesson, Clas
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p. 241 - 255
(2013/06/04)
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- AMINE DERIVATIVES AS POTASSIUM CHANNEL BLOCKERS
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The present invention relates to compounds useful in the modulation of potassium channel activity in cells, in particular the activity of Kv1.3 channels found in T cells. The invention also relates to the use of these compounds in the treatment or prevention of autoimmune and inflammatory diseases, including multiple sclerosis, pharmaceutical compositions containing these compounds and methods for their preparation.
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Page/Page column 86
(2015/09/10)
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- BENZOFURAN AND BENZOTHIOPHENE DERIVATIVES USEFUL IN THE TREATMENT OF CANCERS OF THE CENTRAL NERVOUS SYSTEM
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The present invention relates to benzofuran and benzothiophene derivatives and compositions containing such compounds for the production of medicaments for the treatment of cancers of the central nervous system as monotherapy or combination with other agents.
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Page/Page column 42-43
(2008/06/13)
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- BENZOFURAN DERIVATIVES USEFUL FOR TREATING HYPER-PROLIFERATIVE DISORDERS
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The invention relates to novel heterocycles of formula (I), processes for their preparation and their use for preparing medicaments for the treatment or prophylaxis of disorders, especially of hyperproliferative disorders.
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Page/Page column 97-98
(2008/06/13)
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- BENZOFURAN AND BENZOTHIOPHENE DERIVATIVES USEFUL IN THE TREATMENT OF HYPER-PROLIFERATIVE DISORDERS
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This invention relates to novel benzofuran and benzothiophene derivatives of the general formula and their use for the treatment of hyper-proliferative disorders.
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Page/Page column 20-21
(2008/06/13)
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