Chemical Works of Gedeon Richter Plc, 30-32 Gyömrői Street, Budapest H-1103, Hungary.
Chemical Works of Gedeon Richter Plc, 30-32 Gyömrői Street, Budapest H-1103, Hungary.
Bioorg Med Chem Lett. 2022 Jul 1;67:128714. doi: 10.1016/j.bmcl.2022.128714. Epub 2022 Apr 1.
The systemic use of GABA orthosteric agonist baclofen might be limited due to its detrimental properties: sedation and motor impairment. In contrast, GABA positive allosteric modulators produce less adverse effects. Using BHF-177 as a starting point, we found a new active scaffold: the 6-aryl-quinazoline scaffold. Further elaborating the scaffold, we identified several in vitro and in vivo active compounds.
由于全身性使用 GABA 正位激动剂巴氯芬可能会产生镇静和运动障碍等有害作用，其应用受到限制。相比之下，GABA 正变构调节剂产生的不良反应较少。以 BHF-177 为起始点，我们发现了一个新的活性支架：6-芳基喹唑啉支架。进一步阐述该支架，我们确定了几种具有体外和体内活性的化合物。
