Siebeneicher Holger, Bauser Marcus, Buchmann Bernd, Heisler Iring, Müller Thomas, Neuhaus Roland, Rehwinkel Hartmut, Telser Joachim, Zorn Ludwig
Bayer Pharma AG, Drug Discovery, Medicinal Chemistry 3, Muellerstraße 178, 13353 Berlin, Germany.
Bayer Pharma AG, Drug Discovery, Medicinal Chemistry 3, Muellerstraße 178, 13353 Berlin, Germany.
Bioorg Med Chem Lett. 2016 Apr 1;26(7):1732-7. doi: 10.1016/j.bmcl.2016.02.050. Epub 2016 Feb 19.
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.
通过高通量筛选（HTS）确定，1H-吡唑并[3,4-d]嘧啶类化合物是易化葡萄糖转运蛋白1（GLUT1）的强效抑制剂。对分子骨架的每个环系统进行了广泛的构效关系研究（SAR），揭示了关键的结构基序（即邻甲氧基取代苯、哌嗪和嘧啶）。对GLUT2的选择性极佳，初步的体外和体内药代动力学（PK）研究结果令人鼓舞。
