Identification of novel GLUT inhibitors. Issue 7 (1st April 2016)

• Record Type: Journal Article
• Authors: Siebeneicher, Holger; Bauser, Marcus; Buchmann, Bernd; Heisler, Iring; Müller, Thomas; Neuhaus, Roland; Rehwinkel, Hartmut; Telser, Joachim; Zorn, Ludwig
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 7(2016)
• Page Start: 1732
• Page End: 1737
• Publication Date: 2016-04-01
• Subjects: DXJIXNIYGMNIFL-UHFFFAOYSA-N; GLUT1 inhibitor -- Pyrazolopyrimidine -- Warburg effect -- Structure–activity relationships (SAR) -- In vitro pharmacokinetics (PK); Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.02.050
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: The compound class of 1 H -pyrazolo[3, 4- d ]pyrimidines was identified using HTS as very potent inhibitors of facilitated glucose transporter 1 (GLUT1). Extensive structure–activity relationship studies (SAR) of each ring system of the molecular framework was established revealing essential structural motives (i.e., ortho -methoxy substituted benzene, piperazine and pyrimidine). The selectivity against GLUT2 was excellent and initial in vitro and in vivo pharmacokinetic (PK) studies are encouraging.