Department of Organic Chemistry, Pharmaceutical Faculty, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780 Poznań, Poland.
Int J Mol Sci. 2018 Apr 6;19(4):1104. doi: 10.3390/ijms19041104.
The design and discovery of novel drug candidates are the initial and most probably the crucial steps in the drug development process. One of the tasks of medicinal chemistry is to produce new molecules that have a desired biological effect. However, even today the search for new pharmaceuticals is a very complicated process that is hard to rationalize. Literature provides many scientific reports on future prospects of design of potentially useful drugs. Many trends have been proposed for the design of new drugs containing different structures (dimers, heterodimers, heteromers, adducts, associates, complexes, biooligomers, dendrimers, dual-, bivalent-, multifunction drugs and codrugs, identical or non-identical twin drugs, mixed or combo drugs, supramolecular particles and various nanoindividuals. Recently much attention has been paid to different strategies of molecular hybridization. In this paper, various molecular combinations were described e.g., drug-drug or drug-non-drug combinations which are expressed in a schematic multi-factor form called a molecular matrix, consisting of four factors: association mode, connection method, and the number of elements and linkers. One of the most popular trends is to create small-small molecule combinations such as different hybrids, codrugs, drug-drug conjugates (DDCs) and small-large molecule combinations such as antibody-drug conjugates (ADCs), polymer-drug conjugates (PDCs) or different prodrugs and macromolecular therapeutics. A review of the structural possibilities of active framework combinations indicates that a wide range of potentially effective novel-type compounds can be formed. What is particularly important is that new therapeutics can be obtained in fast, efficient, and selective methods using current trends in chemical synthesis and the design of drugs such as the "Lego" concept or rational green approach.
设计和发现新的药物候选物是药物开发过程中的初始步骤，也是最关键的步骤之一。药物化学的任务之一是产生具有所需生物学效应的新分子。然而，即使在今天，寻找新的药物仍然是一个非常复杂的过程，很难合理化。文献提供了许多关于设计有潜在用途药物的未来前景的科学报告。已经提出了许多设计新药物的趋势，这些药物包含不同的结构（二聚体、杂二聚体、杂多体、加合物、缔合物、配合物、生物低聚物、树枝状聚合物、双、二价、多功能药物和共药物、相同或不同的双胞胎药物、混合或组合药物、超分子粒子和各种纳米个体）。最近，人们对分子杂交的不同策略给予了很多关注。在本文中，描述了各种分子组合，例如药物-药物或药物-非药物组合，这些组合以称为分子矩阵的示意多因素形式表示，由四个因素组成：缔合模式、连接方法以及元素和连接剂的数量。最流行的趋势之一是创建小分子-小分子组合，例如不同的杂种、共药物、药物-药物偶联物（DDC）和大-小分子组合，例如抗体-药物偶联物（ADC）、聚合物-药物偶联物（PDC）或不同的前药和大分子治疗药物。对活性框架组合的结构可能性的综述表明，可以形成广泛的潜在有效新型化合物。特别重要的是，可以使用当前化学合成和药物设计的趋势，例如“乐高”概念或合理的绿色方法，以快速、高效和选择性的方法获得新的治疗方法。
