Unveiling dynamics of nitrogen content and selected nitrogen heterocycles in thrombin inhibitors: a ceteris paribus approach

• Published in: Expert Opinion on Drug Discovery
• Main Author: Masand V.H.; Al-Hussain S.; Alzahrani A.Y.; Al-Mutairi A.A.; Sultan Alqahtani A.; Samad A.; Alafeefy A.M.; Jawarkar R.D.; Zaki M.E.A.
• Format: Article
• Language: English
• Published: Taylor and Francis Ltd. 2024
• Online Access: https://www.scopus.com/inward/record.uri?eid=2-s2.0-85196517466&doi=10.1080%2f17460441.2024.2368743&partnerID=40&md5=c5c682f85f46c6cdabcd33af70c5258d

Background: 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. Research design and methods: 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. Results: 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. Conclusions: 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. © 2024 Informa UK Limited, trading as Taylor & Francis Group.