title: Identification of novel GLUT inhibitors.
abstract: The compound class of 1H-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.
authors.affiliation: Bayer Pharma AG, Drug Discovery, Medicinal Chemistry 3, Muellerstraße 178, 13353 Berlin, Germany. Electronic address: holger.siebeneicher@bayer.com.
authors.forename: Holger
authors.initials: H
authors.lastname: Siebeneicher
authors.affiliation: Bayer Pharma AG, Drug Discovery, Medicinal Chemistry 3, Muellerstraße 178, 13353 Berlin, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Bauser
authors.affiliation: Bayer Pharma AG, Drug Discovery, Medicinal Chemistry 3, Muellerstraße 178, 13353 Berlin, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Buchmann
authors.affiliation: Bayer Pharma AG, Drug Discovery, 42096 Wuppertal, Germany.
authors.forename: Iring
authors.initials: I
authors.lastname: Heisler
authors.affiliation: Bayer Pharma AG, Drug Discovery, 42096 Wuppertal, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
authors.affiliation: Bayer Pharma AG, Drug Discovery, Medicinal Chemistry 3, Muellerstraße 178, 13353 Berlin, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Neuhaus
authors.affiliation: Bayer Pharma AG, Drug Discovery, Medicinal Chemistry 3, Muellerstraße 178, 13353 Berlin, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Rehwinkel
authors.affiliation: Bayer Pharma AG, Drug Discovery, 42096 Wuppertal, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Telser
authors.affiliation: Bayer Pharma AG, Drug Discovery, Medicinal Chemistry 3, Muellerstraße 178, 13353 Berlin, Germany.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Zorn
mesh_terms: D000818:Animals; D002460:Cell Line; D055808:Drug Discovery; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008297:Male; D011743:Pyrimidines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D051272:Glucose Transporter Type 1; D011743:Pyrimidines; C027180:7-ketopyrazolo(4,3-d)pyrimidine
keywords: GLUT1 inhibitor; In vitro pharmacokinetics (PK); Pyrazolopyrimidine; Structure–activity relationships (SAR); Warburg effect