144818-75-7Relevant academic research and scientific papers
Design and Structural Characterization of Potent and Selective Inhibitors of Phosphatidylinositol 4 Kinase IIIβ
Rutaganira, Florentine U.,Fowler, Melissa L.,McPhail, Jacob A.,Gelman, Michael A.,Nguyen, Khanh,Xiong, Anming,Dornan, Gillian L.,Tavshanjian, Brandon,Glenn, Jeffrey S.,Shokat, Kevan M.,Burke, John E.
, p. 1830 - 1839 (2016/03/22)
Type III phosphatidylinositol 4-kinase (PI4KIIIβ) is an essential enzyme in mediating membrane trafficking and is implicated in a variety of pathogenic processes. It is a key host factor mediating replication of RNA viruses. The design of potent and specific inhibitors of this enzyme will be essential to define its cellular roles and may lead to novel antiviral therapeutics. We previously reported the PI4K inhibitor PIK93, and this compound has defined key functions of PI4KIIIβ. However, this compound showed high cross reactivity with class I and III PI3Ks. Using structure-based drug design, we have designed novel potent and selective (>1000-fold over class I and class III PI3Ks) PI4KIIIβ inhibitors. These compounds showed antiviral activity against hepatitis C virus. The co-crystal structure of PI4KIIIβ bound to one of the most potent compounds reveals the molecular basis of specificity. This work will be vital in the design of novel PI4KIIIβ inhibitors, which may play significant roles as antiviral therapeutics.
2-Alkyloxazoles as potent and selective PI4KIIIβ inhibitors demonstrating inhibition of HCV replication
Keaney, Erin P.,Connolly, Michael,Dobler, Markus,Karki, Rajeshri,Honda, Ayako,Sokup, Samantha,Karur, Subramanian,Britt, Shawn,Patnaik, Anup,Raman, Prakash,Hamann, Lawrence G.,Wiedmann, Brigitte,Lamarche, Matthew J.
, p. 3714 - 3718 (2014/09/17)
Synthesis and SAR of 2-alkyloxazoles as class III phosphatidylinositol-4- kinase beta (PI4KIIIβ) inhibitors is described. These compounds demonstrate that inhibition of PI4KIIIβ leads to potent inhibition of HCV replication as observed in genotype (GT) 1a and 1b replicon and GT2a JFH1 virus assays in vitro.
Novel phenoxyalkylamine derivatives. VII. Synthesis and pharmacological activities of 2-alkoxy-5-[(phenoxyalkylamino)alkyl]benzenesulfonamide derivatives
Sakurai,Mitani,Hashimoto,Morikawa,Yasuda,Koshinaka,Kato,Ito
, p. 1443 - 1451 (2007/10/02)
To find a novel α-blocker with high α-blocking selectivity against dopamine D2-receptor affinity, we performed structural modification of the alkylene chains and the substituents on two benzene rings of 2-alkoxy-5-[(phenoxyalkylamino)alkyl]benzenesulfonamide derivatives. The modification of the alkylene chain between the amino moiety in the center of the molecule and the benzene ring (ring A) was found to be the most significant. 5-[2-[[2-(5-Fluoro-2-methoxyphenoxy)ethyl]amino]propyl]-2-methoxybenze nesulfonamide (II-4), which possesses 1-methylethyl as the alkylene chain, exhibited high α-blocking selectivity as well as potent α-blocking activity.
