Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, Julius Maximilian University of Würzburg, Am Hubland, 97074, Würzburg, Germany.
Pharmaceutical and Medicinal Chemistry, Institute of Pharmacy and Food Chemistry, Julius Maximilian University of Würzburg, Am Hubland, 97074, Würzburg, Germany.
Eur J Med Chem. 2019 Oct 15;180:690-706. doi: 10.1016/j.ejmech.2019.07.040. Epub 2019 Jul 12.
In this review, we present the latest advances in the field of multi-target-directed ligand (MTDL) design for the treatment of various complex pathologies of multifactorial origin. In particular, latest findings in the field of MTDL design targeting both an enzyme and a receptor are presented for different diseases such as Alzheimer's disease (AD), depression, addiction, glaucoma, non-alcoholic steatohepatitis and pain and inflammation. The ethology of the diseases is briefly described, with special emphasis on how the MTDL can evolve into novel therapies that replace the classic pharmacological dogma "one target one disease". Considering the current needs for therapy adherence improvement, it is exposed as from the medicinal chemistry, different molecular scaffolds are studied. With the use of structure activity relationship studies and molecular optimization, new hybrid molecules are generated with improved biological properties acting at two biologically very distinct targets.
在这篇综述中，我们介绍了多靶标导向配体（MTDL）设计领域的最新进展，用于治疗多种多因素起源的复杂疾病。特别是，针对阿尔茨海默病（AD）、抑郁症、成瘾、青光眼、非酒精性脂肪性肝炎以及疼痛和炎症等不同疾病，介绍了针对酶和受体的 MTDL 设计的最新发现。简要描述了疾病的发病机制，并特别强调了 MTDL 如何演变为新的治疗方法，从而取代经典的药理学教条“一个靶点一种疾病”。鉴于目前对改善治疗依从性的需求，从药物化学的角度来看，研究了不同的分子骨架。通过使用构效关系研究和分子优化，生成了具有改善的生物特性的新型杂合分子，作用于两个生物学上非常不同的靶标。
