双目标抗肿瘤药物发现的脚手架跳跃方法：机遇和挑战
Scaffold hopping approaches for dual-target antitumor drug discovery: opportunities and challenges
影响因子:4.90000
分区:医学2区 / 药学2区
发表日期:2024 Nov
作者:
Anshul Mishra, Amandeep Thakur, Ram Sharma, Raphael Onuku, Charanjit Kaur, Jing Ping Liou, Sung-Po Hsu, Kunal Nepali
摘要
脚手架跳跃已经成为一种实用策略，可以丰富小分子抗肿瘤剂的合成库。具体而言，它使化学家能够完善铅化合物的药效，药代动力学和生理化学特性。脚手架跳跃为已建立的专利化学领域开辟了新的分子领域。较小的修改，结构刚化和简化（插入环和开放）以及完整的结构大修是药物化学家采用的策略来产生双功能抑制剂的库。此外，该综述概述了脚手架跳跃（软件和程序）的计算方法以及利用有机化的催化作用，用于合成通过脚手架跳跃设计的模板。药物化学家在提供双重抑制性抗肿瘤化学体系中表现出了极大的实力。基于脚手架的药物设计策略产生了大量药物动力学上的双重调节抗肿瘤剂。需要一种涉及计算进步，合成方法进步和常规药物设计策略的综合方法，以增加脚手架辅助药物发现运动的数量。
Abstract
Scaffold hopping has emerged as a practical tactic to enrich the synthetic bank of small molecule antitumor agents. Specifically, it enables the chemist to refine the lead compound's pharmacodynamic, pharmacokinetic, and physiochemical properties. Scaffold hopping opens up fresh molecular territory beyond established patented chemical domains.The authors present the scaffold hopping-based drug design strategies for dual inhibitory antitumor structural templates in this review. Minor modifications, structure rigidification and simplification (ring-closing and opening), and complete structural overhauls were the strategies employed by the medicinal chemist to generate a library of bifunctional inhibitors. In addition, the review presents an overview of the computational methods of scaffold hopping (software and programs) and organopalladium catalysis leveraged for the synthesis of templates designed via scaffold hopping.The medicinal chemist has demonstrated remarkable prowess in furnishing dual inhibitory antitumor chemical architectures. Scaffold hopping-based drug design strategies have yielded a plethora of pharmacodynamically superior dual modulatory antitumor agents. An integrated approach involving computational advancements, synthetic methodology advancements, and conventional drug design strategies is required to increase the number of scaffold-hopping-assisted drug discovery campaigns.