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

IF 6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Expert Opinion on Drug Discovery Pub Date : 2024-08-01 Epub Date: 2024-06-19 DOI:10.1080/17460441.2024.2368743
Vijay H Masand, Sami Al-Hussain, Abdullah Y Alzahrani, Aamal A Al-Mutairi, Arwa Sultan Alqahtani, Abdul Samad, Ahmed M Alafeefy, Rahul D Jawarkar, Magdi E A Zaki
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引用次数: 0

Abstract

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.

揭示凝血酶抑制剂中氮含量和所选氮杂环的动态变化:一种 "雌雄各半 "的方法。
背景: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,但仍亟需优化工作,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,对凝血酶抑制剂中的氮和 N-杂环进行务实的分析在整个药物研发过程中都非常重要。在本研究中,作者进行了一项分析,重点是了解凝血酶抑制剂中氮和特定 N-杂环的发生和分布情况:研究设计:作者利用由 4359 种凝血酶抑制剂组成的数据集,仔细研究了氮原子的各种类别,如环状、非环状、芳香族和非芳香族。此外,还分析了部分芳香族和脂肪族 N-杂环:分析表明,约 62% 的凝血酶抑制剂拥有五个或更少的氮原子。取代的 N-杂环在凝血酶抑制剂中出现率较高,如吡咯烷(23.24%)、吡啶(20.56%)、哌啶(16.10%)、噻唑(9.61%)、咪唑(7.36%)等:结论:大多数活性凝血酶抑制剂含有接近 5 的氮原子以及吡咯烷、吡啶、哌啶等 N-杂环的组合。这项分析为优化先导化合物转化为潜在的抗凝血酶抑制剂提供了重要见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
10.20
自引率
1.60%
发文量
78
审稿时长
6-12 weeks
期刊介绍: Expert Opinion on Drug Discovery (ISSN 1746-0441 [print], 1746-045X [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on novel technologies involved in the drug discovery process, leading to new leads and reduced attrition rates. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering chemoinformatics; bioinformatics; assay development; novel screening technologies; in vitro/in vivo models; structure-based drug design; systems biology Drug Case Histories examining the steps involved in the preclinical and clinical development of a particular drug The audience consists of scientists and managers in the healthcare and pharmaceutical industry, academic pharmaceutical scientists and other closely related professionals looking to enhance the success of their drug candidates through optimisation at the preclinical level.
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