■尽管在理解与凝血酶抑制相关的分子设计原理和生化过程方面取得了进展,迫切需要优化工作并减少合成测试周期的重复。氮和N-杂环是许多抗凝血酶药物的关键特征。因此,在整个药物发现过程中,对凝血酶抑制剂中的氮和N-杂环进行实用分析是很重要的。在目前的工作中,作者提出了一项分析,重点是了解凝血酶抑制剂领域中氮和所选N-杂环的发生和分布。
■包含4359种凝血酶抑制剂的数据集用于仔细检查各种类别的氮原子,例如环,非环,芳香,和非芳香。此外,已分析了选定的芳香族和脂肪族N-杂环。
■分析表明约62%的凝血酶抑制剂具有5个或更少的氮原子。取代的N-杂环有很高的发生率,如吡咯烷(23.24%),吡啶(20.56%),哌啶(16.10%),噻唑(9.61%),咪唑(7.36%),等。在凝血酶抑制剂中。
■大多数活性凝血酶抑制剂含有接近5的氮原子和N-杂环的组合,如吡咯烷,吡啶,哌啶,等。该分析为优化先导化合物向潜在抗凝血酶抑制剂的转化提供了重要见解。
UNASSIGNED: Despite the progress in comprehending molecular design principles and biochemical processes associated with thrombin inhibition, there is a crucial need to optimize efforts and curtail the recurrence of synthesis-testing cycles. Nitrogen and N-heterocycles are key features of many anti-thrombin drugs. Hence, a pragmatic analysis of nitrogen and N-heterocycles in thrombin inhibitors is important throughout the drug discovery pipeline. In the present work, the authors present an analysis with a specific focus on understanding the occurrence and distribution of nitrogen and selected N-heterocycles in the realm of thrombin inhibitors.
UNASSIGNED: A dataset comprising 4359 thrombin inhibitors is used to scrutinize various categories of nitrogen atoms such as ring, non-ring, aromatic, and non-aromatic. In addition, selected aromatic and aliphatic N-heterocycles have been analyzed.
UNASSIGNED: The analysis indicates that ~62% of thrombin inhibitors possess five or fewer nitrogen atoms. Substituted N-heterocycles have a high occurrence, like pyrrolidine (23.24%), pyridine (20.56%),
piperidine (16.10%), thiazole (9.61%), imidazole (7.36%), etc. in thrombin inhibitors.
UNASSIGNED: The majority of active thrombin inhibitors contain nitrogen atoms close to 5 and a combination of N-heterocycles like pyrrolidine, pyridine,
piperidine, etc. This analysis provides crucial insights to optimize the transformation of lead compounds into potential anti-thrombin inhibitors.