GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park (North), Coldharbour Road, Harlow, Essex CM19 5AD, England, United Kingdom.
Bioorg Med Chem Lett. 2009 Feb 1;19(3):990-4. doi: 10.1016/j.bmcl.2008.11.064. Epub 2008 Nov 24.
A novel oxytocin antagonist was identified by 'scaffold-hopping' using Cresset FieldScreen molecular field similarity searching. A single cycle of optimization driven by an understanding of the key pharmacophoric elements required for activity led to the discovery of a potent, selective and highly ligand-efficient oxytocin receptor antagonist. Selectivity over vasopressin receptors was rationalized based on differences in the structure of the natural ligands.
通过使用 Cresset FieldScreen 分子场相似性搜索的“支架跳跃”方法，鉴定出一种新型的催产素拮抗剂。在对活性所需的关键药效团元素有了深入了解的基础上，通过一轮优化循环，发现了一种强效、选择性和高配体效率的催产素受体拮抗剂。基于天然配体结构的差异，对血管加压素受体的选择性得到了合理的解释。
