248269-97-8Relevant academic research and scientific papers
Rational Design and Synthesis of Selective PRMT4 Inhibitors: A New Chemotype for Development of Cancer Therapeutics**
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
supporting information, p. 1116 - 1125 (2021/03/08)
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.
Discovery of a rapidly metabolized, long-acting β2 adrenergic receptor agonist with a short onset time incorporating a sulfone group suitable for once-daily dosing
Procopiou, Panayiotis A.,Barrett, Victoria J.,Biggadike, Keith,Butchers, Peter R.,Craven, Andrew,Ford, Alison J.,Guntrip, Stephen B.,Holmes, Duncan S.,Hughes, Sara C.,Jones, Anne E.,Looker, Brian E.,Mutch, Peter J.,Ruston, Mark,Needham, Deborah,Smith, Claire E.
, p. 159 - 170 (2014/02/14)
A series of novel, potent, and selective human β2 adrenoceptor agonists incorporating a sulfone moiety on the terminal right-hand-side phenyl ring of (R)-salmeterol is presented. Sulfone 10b had salmeterol-like potency and selectivity profile, long duration of action on guinea pig trachea, and longer than salmeterol duration of action in vivo, suitable for once-daily dosing. It had lower than salmeterol oral absorption in rat, lower bioavailability in rat and dog, and a high turnover in human hepatocytes. It was metabolized in human hepatocytes by hydroxylation, oxidation, cleavage, and conjugation; most of the metabolites would be expected to have reduced or no β2 activity. The 4-biphenylsulfonic acid was identified as a crystalline, non-hygroscopic salt of 10b, suitable for inhaled delivery. Furthermore, it was free of any genetic toxicity issues and was considered as a backup to vilanterol.
PHENETHANOLAMINE DERIVATIVE FOR THE TREATMENT OF RESPIRATORY DISEASES
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Page 55, (2010/02/06)
The present invention relates to novel compounds of formula (I), to a process for their manufacture, to pharmaceutical compositions containing them, and to their use in therapy, in particular their use in the prophylaxis and treatment of respiratory diseases.
