发现苯甲酰基异吲哚啉是一类新型强效、选择性和口服活性 GlyT1 抑制剂。
Discovery of benzoylisoindolines as a novel class of potent, selective and orally active GlyT1 inhibitors.
机构信息
F. Hoffmann-La Roche Ltd, Pharmaceutical Research Basel, Basel, Switzerland.
出版信息
Bioorg Med Chem Lett. 2010 Dec 1;20(23):6960-5. doi: 10.1016/j.bmcl.2010.09.124. Epub 2010 Oct 7.
PMID:20974532
Abstract
Benzoylisoindolines were discovered as a novel structural class of GlyT1 inhibitors. SAR studies and subsequent lead optimization efforts focused primarily on addressing hERG liability and on improving in vivo efficacy resulted in the identification of potent GlyT1 inhibitors displaying excellent selectivity and in vivo PD and PK profiles.
摘要
苯甲酰基异吲哚啉被发现是一种新型甘氨酸转运体 1（GlyT1）抑制剂结构类别。构效关系研究和随后的先导化合物优化工作主要集中在解决 hERG 相关毒性和提高体内疗效上，最终确定了具有良好选择性和体内药效学、药代动力学特征的有效 GlyT1 抑制剂。
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